Tesis sobre el tema "Focal cerebral ischemia"
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1
Thorén, Anna. "Astrocyte metabolism following focal cerebral ischemia /". Göteborg : Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Göteborg University, 2006. http://hdl.handle.net/2077/744.
2
Christensen, Thomas. "Experimental focal cerebral ischemia : pathophysiology, metabolism and pharmacology of the ischemic penumbra /". Copenhagen, 2007. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=016143698&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
3
Ng, Kit-ying. "Neuroprotective effects of adiponectin in focal cerebral ischemia". Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39634371.
4
Ng, Kit-ying y 吳潔瑩. "Neuroprotective effects of adiponectin in focal cerebral ischemia". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39634371.
5
Ward, Nicholas M. "The assessment of behavioural deficits following focal cerebral ischemia". Thesis, University of St Andrews, 1997. http://hdl.handle.net/10023/14698.
Resumen
Evaluating the efficacy of neuroprotective drugs in rat models of focal cerebral ischemia has involved histological and behavioural batteries to examine pathology and sensorimotor function. However, the behavioural tests used provide little insight into the nature of the neurological impairments. In an effort to gain further insight into the behavioural impairment following ischemic lesions, a battery of tasks were used. The tasks included tests of sensorimotor, motor (paw use), motivation, sensory and attentional function. The use of the potent vasoconstrictor endothelin-1 has allowed cerebral arteries to be occluded. This can be used to occlude the MCA (which is a common target of ischemia research), as well as other arteries, such as the ACA. Typically quantitative volumetric analysis has used nissl stains to assess lesion extent. However, alternative markers of tissue dysfunction are available including GFAP to assess the astroglial response to ischemia. Consequently cresyl violet and GFAP were compared along with different methods for calculating lesion volume. The boundaries of the lesion identified using the two stains corresponded closely providing care was taken when calculating lesion volume to avoid distortion from histological procedures and edema. Following MCA occlusion the rats displayed unilateral somatosensory and motor deficits, however there was no evidence of attentional dysfunction. Performance in the covert orienting task was compared with striatal dopamine depletion and with a posterior parietal cortical lesion. Neither of these manipulations resulted in deficits of covert orienting. Furthermore, the behavioural consequences of ACA occlusion were studied in two experiments using reaction time tasks designed to dissociate response impairments from dysfunction of motivation and attention. The ACA ischemic damage did not disrupt motivation or attention, however, the results were consistent with an impairment in selecting and initiating responses.
6
Thomas, Sunu Samuel. "Murine models of cerebral ischemia, development of a mouse model of global cerebral ischemia; response of GluR2 knockout mice in a model of permanent focal cerebral ischemia". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0026/MQ50439.pdf.
7
Davis, Stephanie. "Leukemia Inhibitory Factor as a Neuroprotective Agent against Focal Cerebral Ischemia". Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6218.
Resumen
Previous publications from this laboratory demonstrated that administration of leukemia inhibitory factor (LIF) (125 µg/kg) to young, male Sprague-Dawley rats at 6, 24, and 48 h after middle cerebral artery occlusion (MCAO) reduced infract volume, improved sensimotor skills, and alleviated damage to white matter at 72 h after the injury. In vitro studies using cultured oligodendrocytes (OLs) showed that LIF (200 ng/ml) also protects against 24 h of oxygen-glucose deprivation through activation of Akt signaling and upregulation of the antioxidant enzymes peroxiredoxin IV and metallothionein III. Other groups have demonstrated that LIF reduces neurodegeneration in animal models of disease, but the neuroprotective mechanisms of LIF during permanent ischemia have not yet been examined. The overall hypothesis to be tested in this project is whether LIF exerts similar protective mechanisms against neurons during ischemia through increased antioxidant enzyme expression in neurons.
In the first set of experiments, superoxide dismutase (SOD) activity was significantly increased in the ipsilateral hemisphere of LIF-treated rats compared to rats that received PBS treatment at 72 h after MCAO. Western blot and immunohistochemical analysis revealed that SOD3 was upregulated in brain tissue and induced specifically in cortical neurons tissue at this time point. Neurons that expressed high levels of SOD3 at 72 h after MCAO also showed high levels of phosphorylated Akt (Ser473). LIF (200 ng/ml) reduced necrotic and apoptotic cell death against 24 h of OGD as measured by lactate dehydrogenase (LDH) release and caspase-3 activation. Quantitative real-time PCR analysis showed that LIF treatment upregulated SOD3 gene expression in vitro during OGD. Treatment with 10 µM Akt Inhibitor IV and transfection with SOD3 siRNA counteracted the neuroprotective effects of LIF in vitro, showing that upregulation of SOD3 and activation of Akt signaling are necessary for LIF-mediated neuroprotection.
Several transcription factors that regulated Akt-inducible genes were previously identified by this lab, including myeloid zinc finger-1 (MZF-1) and specificity protein-1 (Sp1). The goal of the second set of experiments was to determine whether LIF exerted protective actions through MZF-1 and Sp1. According to analysis with Genomatix, MZF-1 and Sp1 have multiple binding sites in the promoter for the rat SOD3 gene. Western blot analysis showed that there was a trend towards increased MZF-1 protein expression in the brains of LIF-treated rats that approached significance. Immunohistochemical analysis and quantitative real-time PCR showed a significant in vitro upregulation in MZF-1 expression among LIF-treated neurons compared to PBS-treated neurons. Sp1 gene expression was not changed by LIF treatment, but there was a trend towards increased protein expression. In addition, there was a significant correlation between Sp1 and MZF-1 among brain samples from LIF-treated rats but not PBS-treated or sham rats at 72 h after MCAO. Immunohistochemical analysis revealed that Sp1 and MZF-1 co-localized with neuronal nuclei and SOD3 at 72 h after MCAO. Neurons that were transfected with MZF-1 or Sp1 siRNA following isolation did not show a significant decrease in LDH release after 24 h OGD that was observed among neurons transfected with scrambled siRNA. These data demonstrate that Sp1 and MZF-1 are involved with the neuroprotective signaling of LIF under ischemia.
This laboratory has demonstrated that LIF activates transcription of protective genes and increases the activity of transcription factors through modulation of intracellular signaling. However, the upstream signaling mechanisms of LIF during ischemia had not previously been investigated. Previous investigators found that the LIF-specific subunit of the heterodimeric LIF receptor (LIFR) is induced by CNS injury. Western blot analysis was used to determine whether LIFR was induced in the brain and the spleen, which plays a role in the peripheral immune response, after MCAO. According to these results, LIF treatment significantly upregulates LIF in the brain compared to PBS treatment or sham injury at 72 h after MCAO. Genomatix analysis of the LIFR promoter region revealed a binding site for Sp1, which is one of the transcription factors responsible for neuroprotection by LIF. At this same time point, splenic LIFR expression is significantly reduced after MCAO compared to sham injury. LIF treatment did not significantly increase LIFR expression, but did significantly increase spleen size compared to PBS treatment at 72 h after MCAO. Although there was a trend towards increased LIFR expression in the spleen from 24 h to 72 h after MCAO, this increase was not statistically significant. However, there was a significant positive correlation between spleen weight and LIFR expression among rats euthanized 24-72 h after MCAO/sham injury. In addition, there was a significant negative correlation between LIFR expression in the brain and the spleen weight, thus showing that LIFR is upregulated following the splenic response.
According to findings from other groups, JAK1 has been shown to associate with the heterodimeric LIF receptor (LIFR/gp130) and directly activate PI3K/Akt signaling. To test whether JAK1 contributes neuroprotection during ischemia, cultured neurons were treated with several concentrations (2.5-50 nM) of GLPG0634, a JAK1-specific inhibitor prior to 24 h of OGD. With the exception of the 2.5 nM concentration, all concentrations of GLPG0634 significantly decreased LDH release compared to DMSO treatment, with the 5 nM concentration having the most potent effect on reducing cytotoxicity. However, the 5 nM concentration had no significant did not significantly reduce LDH release compared to DMSO treatment under 24 h of normoxic conditions. These results indicate that JAK1 activity is primarily detrimental to neurons during ischemia. Although it is possible that LIF signaling activates JAK1, it is unlikely that JAK1 is responsible for LIF-mediated neuroprotection during ischemia.
The results of these experiments allowed us to determine several molecular mechanisms for LIF-mediated neuroprotection. LIF, which binds to its heterodimeric receptor, activates Akt signaling during ischemia. The transcription factors Sp1 and MZF-1, which are located downstream of Akt, bind to the promoter of the SOD3 gene. In addition, Sp1 also regulates the LIFR gene. SOD3 upregulation increases total SOD activity, which decreases apoptotic and necrotic cell death during apoptosis. Due to its ability to promote antioxidant expression and survival signaling in multiple neural cell types, LIF shows promise as a novel treatment for permanent focal cerebral ischemia.
8
Leung, Wai-chung. "Investigations into the role of endothelial endothelin-1 on transient focal cerebral ischemia". Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39634127.
9
Leung, Wai-chung y 梁偉聰. "Investigations into the role of endothelial endothelin-1 on transient focal cerebral ischemia". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39634127.
10
Fujimoto, Motoaki. "Tissue inhibitor of metalloproteinases protect blood?brain barrier disruption in focal cerebral ischemia". Kyoto University, 2009. http://hdl.handle.net/2433/124303.
11
Chen, Shaohua. "Role of neuropeptide Y and its receptor analogues in focal cerebral ischemia in the rat". Click to view the E-thesis via HKUTO, 2002. http://sunzi.lib.hku.hk/hkuto/record/B42576738.
12
Jiang, Wei. "Regeneration in the adult brain after focal cerebral ischemia : exploration of neurogenesis and angiogenesis". Doctoral thesis, Umeå : Department of Public Health and Clinical Medicine, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-739.
13
Gerova, Nadezhda [Verfasser]. "Expression of angiotensin receptors in the rat brain after focal cerebral ischemia / Nadezhda Gerova". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1071087770/34.
14
Hattotori, Itaro. "Intravenous Administration of Thioredoxin Decreases Brain Damage Following Transient Focal Cerebral Ischemia in Mice". Kyoto University, 2004. http://hdl.handle.net/2433/147483.
15
Huang, Zhigao. "Implication of anti-apoptotic genes in neuronal death following focal cerebral ischemia in rats". Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6270.
Resumen
Accumulating biochemical and morphological evidence suggests that apoptosis contributes to neuronal cell death following cerebral ischemia. Recent research which has examined changes in expression of proapoptotic proteins has further strengthened the important role of apoptosis in ischemic cell death. In this thesis I first addressed the role of apoptosis in ischemic death by examining p53, which is itself a complex multifunctional tumor suppresser gene, following transient focal ischemia. Of particular note were the alterations of the anti-apoptosic gene, naip, that were observed under stress conditions. The anatomical distribution of naip expression and neuronal survival following middle cerebral artery occlusion (MCA-o) were closely examined. In experiment I, SHR rats were subjected to 90 minute MCA-o followed by 22.5 hr reperfusion (RP) and compared with sham operated controls. In experiment II, sections obtained from fresh frozen or fixed brain tissue of long-Evans hooded rats (n = 3--4) that had been subjected to hippocampal kindling were used for ISHH or immunohistochemistry for naip expression. Neuronal protection against cerebral ischemia by hippocampal kindling was assessed in experiment III. Hippocampal kindled animals were also used to study the time course of naip expression in the frontoparietal cortex, which is mainly supplied by MCA. Both p53 mRNA and protein were elevated in the ischemic penumbra in experiment I. The induction of p53 peaked within 8--12 hr then returned to basal levels within 24 hr after RP. The short duration of p53 induction in ischemic penumbra may suggest that p53 activate downstream genes responsible for growth arrest, DNA repair or/and apoptosis. Experiment II demonstrated a significant elevation in naip mRNA and proteins in piriform cortex and hippocampus, where neuronal populations known to be protected by kindling. The duration of the elevation lasted up to three weeks. In contrast, naip mRNA and protein remained at baseline levels in regions that are not protected, such as endopiriform cortex and medial thalamus. We also demonstrated that hippocampal kindling attenuated cortical infarct induced by MCA-o to 57.7 +/- 4.6mm3 as compared to 156.5 +/- 12.6mm3 in controls. This neuroprotection was associated with a two to three fold elevation of naip expression in the corresponding areas by kindling treatment. (Abstract shortened by UMI.)
16
Chen, Shaohua y 陳韶華. "Role of neuropeptide Y and its receptor analogues in focal cerebral ischemia in the rat". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B42576738.
17
Liu, Lingguang y 刘灵光. "Neuroprotection of melatonin and/or electro-acupuncture in a rat model of focal cerebral ischemia". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hdl.handle.net/10722/198928.
Resumen
Stroke is a serious cerebral vascular event and a leading cause of death and disability worldwide, and ischemic stroke is the most common type. Evidence from animal research in acute cerebral ischemia shows that a combination of neuroprotectants might be more efficacious than the single agent given individually.
Both melatonin and electro-acupuncture (EA) have been suggested to be effective treatments against cerebral ischemia. However, it is unknown whether a combination of these two therapies could be beneficial against focal cerebral ischemia.
In the first study, the effect of post-treatment with a combination of melatonin and EA on regional cerebral blood flow (rCBF), neurological deficit score and infarct volume was investigated in both permanent and transient middle cerebral artery occlusion (MCAO) models in rats. When compared with the single treatment of melatonin or EA, the combination therapy resulted in a significant improvement of neurological function and a dramatic reduction of infarct volume at 72 hr after transient MCAO. A significant upregulatory effect on rCBF has been exerted by the combined treatment.
The effect of a combination of melatonin and EA on inflammatory reaction was investigated in the second study. Post-treatment of the combination therapy effectively inhibited neutrophil infiltration as well as the expression of some pro-inflammatory mediators, and increased the anti-inflammatory protein expression at 72 hr after transient MCAO. This beneficial effect may be due to the respective anti-inflammatory effects of melatonin and EA.
In the third study, the effect of a combination of melatonin and EA on apoptosis was examined. When compared with the EA treatment alone, post-treatment of the combination therapy exerted a greater inhibitory effect on tissue apoptosis and expression of the pro-apoptotic proteins as well as an upregulatory effect on the anti-apoptotic protein expression.
In the fourth study, the effect of continuous post-treatment of a combination of melatonin and EA on transient MCAO was investigated. The combination treatment significantly improved neurological function and decreased infarct volume at 7 days after transient MCAO. Cell proliferation and expression of the neurotrophic factor were increased by the combined treatment.
The effect of pretreatment with a combination of melatonin and EA was examined in the fifth study. Neurological function was improved and infarct volume was reduced by the combination pretreatment at 24 hr after transient MCAO. The inflammatory and apoptotic reaction were inhibited by the combined pretreatment through the modulatory effect of the related proteins.
In summary, our results show that, when compared with the single treatment of either melatonin or EA, post-treatment with a combination of melatonin and EA induced a complementary neuroprotective effect on improvement of neurological function and a dramatic reduction of infarct volume after transient MCAO. The complementary protection may be partially mediated via anti-inflammation and anti-apoptosis after transient cerebral ischemia. Pretreatment with a combination of melatonin and EA may be more effective in preventing ischemic brain injury after transient focal cerebral ischemia.published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
18
Fernandes, Mara Yone Soares Dias. "Efeito neuroprotetor do α-bisabolol em camundongos submetidos à isquemia cerebral focal permanente". Universidade Federal do CearÃ, 2015. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=14886.
Resumen
FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgicoO acidente vascular cerebral (AVE) à uma das principais causa de mortalidade no Brasil, acometendo cerca de 200.000 indivÃduos anualmente. A fisiopatologia do AVE isquÃmico envolve uma complexa cascata de eventos como a inflamaÃÃo e o estresse oxidativo que podem à morte neuronal e dÃficits cognitivos. O α-bisabolol à um Ãlcool sesquiterpeno, monocÃclico, que ocorre na natureza e à encontrado como constituinte majoritÃrio do Ãleo essencial sintÃtico da Matricaria chamomilla, que possui atividade antiinflamatÃria, antioxidante e anti-apoptÃtica jà descritas. Para avaliar o efeito neuroprotetor deste composto em camundongos submetidos à oclusÃo permanente da artÃria cerebral media (pMCAO), os animais foram prà e pÃs tratados com α-bisabolol nas doses de 50, 100 e 200 mg/kg, v.o, durante 24, 48, 72, 96 ou 120 horas apÃs a isquemia. Os animais foram avaliados 24h apÃs a isquÃmia para verificar a Ãrea de lesÃo isquÃmica, avaliaÃÃo neurolÃgica e atividade da mieloperoxidase. 72 horas apÃs a pMCAO, os testes de atividade locomotora, memÃria de trabalho e memÃria aversiva recente foram realizados. 96 horas apÃs a pMCAO foi realizado o teste do reconhecimento de objecto, e os animais foram eutanasiados para a realizaÃÃo da Imunohistoquimica para TNF-α, iNOS e GFAP e anÃlise histologica para Cresil violeta e Fluoro Jade C. Finalmente, 120h apÃs a isquemia, avaliou-se a memÃria espacial. O α-bisabolol reduziu significativamente a lesÃo isquemica e o dÃficit neurolÃgico e normalizou a atividade locomotora. O α-bisabolol mostrou proteÃÃo contra os dÃficits nas memÃrias de trabalho, espacial, reconhecimento de objeto e aversiva. O α-bisabolol (200 mg/kg) preveniu significativamente o aumento da MPO e TNF-α no cÃrtex temporal e o aumento do iNOS tanto no cÃrtex temporal como no estriado. Tambem preveniu o aumento da astrogliose nessas Ãreas. O α-bisabolol (200 mg/kg) mostrou protecÃÃo contra a morte neuronal. Os resultados do presente estudo mostraram que o α-bisabolol possui atividade neuroprotetora provavelmente devido a sua aÃÃo antiinflamatÃria, mas outros mecanismos nÃo podem ser descartados.
Stroke is the leading cause of mortality in Brazil, affecting about 200,000 individuals annually. The pathophysiology of ischemic stroke involves a complex cascade of events such as inflammation and oxidative stress which will lead to neuronal death and cognitive deficits. The α-bisabolol is a sesquiterpene alcohol, natural, monocyclic, found as main constituents of the essential oil of Matricaria chamomilla, which has anti-inflammatory, antioxidant and anti-apoptotic already described. To evaluate the neuroprotective effects of this compound in mice underwent permanent occlusion of the middle cerebral artery (pMCAO), the animals were pre and post treated with α-bisabolol at doses of 50, 100 and 200 mg / kg, orally for 24, 48, 72, 96 or 120 hours after pMCAO. The animals were evaluated 24 hours after ischemia to verify the area of ischemic damage, and neurological evaluation and myeloperoxidase activity. Seventy-two hours after pMCAO, the locomotor activity tests, working memory and aversive recent memory were performed. Ninety six hours after the pMCAO was performed the object recognition test, and the animals were euthanized for carrying out the immunohistochemistry for TNF-α, iNOS and GFAP and for histology analyes Cresil violet and Fluoro Jade C. Finally, 120 h after pMCAO, the spatial memory was evaluated. The α-bisabolol reduced significantly ischemic damage and neurological deficit and normalized the locomotor activity. The α-bisabolol showed protection against the deficits in working, spatial, object recognition and aversive memories. The α-bisabolol (200 mg / kg) significantly prevented the increase of MPO and TNF-α in the temporal cortex and the increased of iNOS both in the temporal cortex and in striatum. Also prevented the increase in astrogliosis in there area. The α-bisabolol (200 mg / kg) showed protection against neuronal death. The results of this study showed that α-bisabolol has neuroprotective activity probably due to its anti-inflammatory action, but other mechanisms can not be discarded.
19
Farrokhnia, Nasim. "Hyperglycemia and Focal Brain Ischemia : Clinical and Experimental Studies". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5938.
20
Lennmyr, Fredrik. "Signal Transduction in Focal Cerebral Ischemia : Experimental Studies on VEGF, MAPK and Src family kinases". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5267-1/.
21
Hase, Yoshiki. "Cilostazol, a phosphodiesterase inhibitor, prevents no-reflow and hemorrhage in mice with focal cerebral ischemia". Kyoto University, 2012. http://hdl.handle.net/2433/157459.
22
Sicard, Kenneth M. "Multimodal MRI, Behavioral Testing, and Histology in a Rat Model of Transient Focal Cerebral Ischemia : A Dissertation". eScholarship@UMMS, 2006. http://escholarship.umassmed.edu/gsbs_diss/318.
Resumen
Cerebral ischemia is defined as a decrease in blood flow to the brain. It is most often caused by obstruction of a cerebral blood vessel, and is recognized by the World Health Organization as the leading cause of serious adult disability and one of the top three causes of adult death worldwide. Most survivors demonstrate partial restitution of function over time, but the underlying recovery mechanism(s) remain unclear especially in a subset of patients with persistent neurological morbidities despite normal-appearing brain on neuroimaging. The optimal way to understand any human disease state is via clinical studies. Unfortunately, well-controlled experiments in humans are difficult due to small patient populations, the presence of numerous confounding variables, and ethical issues associated with invasive or discomforting experimental procedures. Anesthetized animal models of cerebral ischemia afford a means of avoiding the above difficulties. However, anesthesia and physiological perturbations that occasionally follow brain ischemia may affect the reliability of certain tools used to study this disease, such as functional magnetic resonance imaging (fMRI). Therefore, the central goals of this thesis were: 1) to evaluate the feasibility of performing fMRI in anesthetized and awake animals, 2) to assess fMRI responses under various perturbations of cerebral perfusion and tissue oxygenation in order to identify key factors that may modulate functional signal changes following ischemia, and 3) to utilize fMRI, behavioral tests and histology in an anesthetized animal model of transient focal cerebral ischemia to explore postischemic changes in brain pathology/function and how they relate to changes in behavior.
In the first study of this dissertation, I report the evaluation of fMRI responses in anesthetized and awake animals. Anesthesia is frequently used in animal models of cerebral ischemia, but is known to alter brain perfusion and metabolism which may, in turn, affect fMRI responsivity. Perfusion-based fMRI was used to evaluate cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) responses to hypercapnia in awake and isoflurane-anesthetized rats. Hypercapnia produced significant CBF and BOLD fMRI signal changes throughout the cerebrum in awake and isoflurane-anesthetized groups. These results show that perfusion-based fMRI can successfully detect stimulus-evoked hemodynamic changes in the brains of both conscious and isoflurane-anesthetized animals.
The second study of this dissertation: 1) investigates the effects of alterations in cerebral perfusion and oxygenation on fMRI signal changes, and 2) examines the self-consistency of an imaging-based formalism for the calculation of the cerebral metabolic rate of oxygen (CMRO2). Functional MRI responses to a stimulus can be described in terms of relative or absolute signal change. A relative fMRI response is defined as a percent-change relative to its own respective baseline value. An absolute fMRI response is defined as a quantitative change relative to a single fixed baseline value that serves as a control. Thus, an absolute fMRI signal change is largely independent of the baseline state and may more accurately index brain activity when baseline fMRI signals change significantly over time due to, for example, hemodynamic-metabolic disturbances that occur during and/or after brain ischemia. To address these issues, the effects of inspired hypoxic, normoxic, hyperoxic, and hypercapnic gases on baseline and forepaw stimulation-evoked changes in BOLD and CBF fMRI signals were examined in isoflurane-anesthetized rats. Relative fMRI responses to forepaw stimulation varied-whereas. absolute responses were similar--across gas conditions. These results demonstrate that absolute measurements of fMRI signal change may lend a more accurate measure of brain activity during states of altered basal physiology as well as support the self-consistency of the imaging-based CMRO2 formalism under these conditions.
The third and last study of this dissertation utilized multimodal MRI, behavioral tests, and histology at acute to chronic periods following transient middle cerebral artery occlusion (tMCAO) in the rat to examine the evolution of pathological, functional, and behavioral parameters following transient focal cerebral ischemia. MRI was used to track the evolution of brain pathology and function following cerebral ischemia, and it was found that the cerebral sensorimotor network, critical for sensory and motor behavioral functions, showed profoundly abnormal signal changes that required up to one day to normalize. Adhesive removal, forepaw placement and beam-walk behavioral tests demonstrated sensorimotor dysfunctions that gradually improved but remained long after the recovery of MRI parameters. Postmortem histology confirmed the presence of selective neural cell death within the sensorimotor network at time points when behavior was abnormal. These results suggest that subtle postischemic pathological changes in the brain undetectable by MRI may be responsible for persistent behavioral deficits-a finding which may be relevant to a clinical subset of patients with persistent neurological morbidities despite negative MRI results following cerebral ischemia.
23
Theodorsson, Annette. "Estrogen-inducible neuropeptides in the rat brain : role in focal ischemic lesions /". Doctoral thesis, Linköping : Linköpings universitet, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-4716.
24
Hamzei, Taj Somayyeh [Verfasser] y Heike [Gutachter] Endepols. "MicroRNA-induced polarization of microglia and macrophages after focal cerebral ischemia / Somayyeh Hamzei Taj. Gutachter: Heike Endepols". Köln : Universitäts- und Stadtbibliothek Köln, 2016. http://d-nb.info/1106380916/34.
25
Dezena, Roberto Alexandre. "Neuroproteção hipotérmica pré, intra e pós-isquêmica na isquemia cerebral focal temporária em ratos: análise morfométrica". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-08022011-132753/.
Resumen
INTRODUÇÃO: A isquemia cerebral é uma doença de alta prevalência, com desfecho clínico imprevisível, e com profilaxia e tratamento ainda limitados. Na atividade neurocirúrgica, as duas situações em que a isquemia cerebral ocorre com maior freqüência são o vasoespasmo arterial, que ocorre após hemorragia subaracnóidea, e nas microneurocirurgias vasculares, especialmente naquelas em que são realizadas clipagens vasculares temporárias. Dentre todas as formas de neuroproteção a hipotermia tem se mostrado a mais promissora em estudos experimentais. Pode ser aplicada em diferentes momentos do processo isquêmico (pré, intra ou pós-isquemia), sendo a modalidade pré-isquêmica pouco explorada na literatura. O objetivo deste estudo foi avaliar comparativamente o efeito da hipotermia pré, intra e pós-isquêmica na isquemia focal temporária por oclusão da artéria cerebral média em ratos, através de análise morfométrica computacional. MATERIAL E MÉTODOS: Foram utilizados 74 ratos machos adultos da linhagem Wistar, divididos em 6 grupos, com 10 animais cada: Controle (C), Sham (S), Controle-Isquêmico (CI), Hipotermia Pré-Isquêmica (IH1), Hipotermia Intra-Isquêmica (IH2), Hipotermia Pós-Isquêmica (IH3). Todos os animais dos grupos isquêmicos foram submetidos à isquemia de 60 minutos, com um período reperfusional de 24 horas. A hipotermia utilizada foi do tipo leve (32 - 34 ºC). No grupo IH1 a hipotermia foi iniciada 30 min antes da oclusão arterial e mantida durante toda a isquemia; no grupo IH2 a hipotermia foi mantida somente durante a isquemia; no grupo IH3 a hipotermia foi mantida por 6 horas, sendo iniciada no exato momento da reperfusão. Após a eutanásia os cérebros foram perfundidos e fixados, sendo realizadas secções coronais de 10 micrômetros, em toda a extensão da área isquêmica, as quais foram coradas pela técnica Luxol Fast Blue. A morfometria foi realizada pelo programa KS400, Carl Zeiss, obtendo-se medidas diretas separadas de cada hemisfério, das áreas em azul (fibras mielinizadas) e em vermelho (corpos neuronais), bem como a área total de cada secção. Medidas derivadas (área isquêmica média, e volumes isquêmicos parcial e aproximado) de cada animal, foram obtidas nos grupos submetidos à isquemia. RESULTADOS: Os parâmetros da homeostase dos animais permaneceram dentro dos limites aceitáveis para este tipo de experimento. Em relação às áreas de fibras mielinizadas (azul) não houve diferença significativa entre os grupos C vs. S (p=0,39, Mann-Whitney-Wilcoxon), CI vs. IH3 (p=0,85, Mann-Whitney-Wilcoxon), e IH1 vs. IH2 (p=0,63, Mann-Whitney-Wilcoxon); ocorreu diferença estatística entre os grupos C vs. CI (p=0,0001, Mann-Whitney-Wilcoxon), CI vs. IH1 (p=0,01, Mann-Whitney-Wilcoxon), e CI vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). Em relação às áreas de corpos neuronais (vermelho), não houve diferença significativa entre os grupos C vs. S (p=0,48, Mann-Whitney-Wilcoxon), CI vs. IH3 (p=0,27, Mann-Whitney-Wilcoxon), e IH1 vs. IH2 (p=0,68, Mann-Whitney-Wilcoxon); ocorreu diferença estatística entre os grupos C vs. CI (p=0,0001, Mann-Whitney-Wilcoxon), CI vs. IH1 (p=0,009, Mann-Whitney-Wilcoxon), e CI vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). A análise estatística das áreas isquêmicas médias, e dos volumes isquêmicos parciais e aproximados não mostrou diferença significante na comparação entre os grupos CI vs. IH3 (p=0,57, Mann-Whitney-Wilcoxon), e IH1 vs. IH2 (p=0,79, Mann-Whitney-Wilcoxon); mostrou diferença significante entre os grupos CI vs. IH1 (p=0,0001, Mann-Whitney-Wilcoxon), e CI vs. IH2 (p=0,0011, Mann-Whitney-Wilcoxon). CONCLUSÕES: As hipotermias pré-isquêmica e intra-isquêmica mostraram-se neuroprotetoras de forma semelhante, o que não ocorreu com a hipotermia pós-isquêmica.INTRODUCTION: Cerebral ischemia is a high prevalent disease, with unpredictable clinical outcome, and prophylaxis and treatment remains limited. In the neurosurgical practice cerebral ischemia occurs most frequently due arterial vasospasm after subarachnoid hemorrhage, and in vascular microneurosurgery, mainly when temporary vascular clipping is performed. Among all forms of experimental neuroprotection, hypothermia has been the most promising. It can be applied at different moments of ischemia (pre, intra or post-ischemia), and the pre-ischemic modality is little explored in literature. This study aimed to evaluate comparatively the effect of pre, intra and post-ischemic hypothermia in temporary focal ischemia obtained by middle cerebral artery occlusion in rats, by computational morphometric analysis. MATERIAL AND METHODS: We used 74 Wistar adult male rats divided into six groups of 10 animals each: Control (C), Sham (S), Ischemic-Control (IC), Pre-Ischemic Hypothermia (IH1), Intra-Ischemic Hypothermia (IH2), Post-Ischemic Hypothermia (IH3). All animals in the ischemic groups were subjected to ischemia for 60 minutes with a reperfusion period of 24 hours. It was used mild hypothermia (32 - 34 ºC). In IH1 group hypothermia was initiated 30 minutes before arterial occlusion and maintained throughout the ischemia, in IH2 group hypothermia was maintained only during ischemia, IH3 group hypothermia was maintained for 6 hours, starting at the beginning of the reperfusion. After euthanasia, the brains were perfused and fixed, and coronal sections of 10 microns were performed to the fullest extent of ischemic area, and these sections were stained by Luxol Fast Blue. The morphometry was performed by the KS400 software, Carl Zeiss, obtaining direct separated measurements in each hemisphere, of blue areas (myelinated fibers) and red areas (neuronal bodies) as well as the total area of each section. Derived measures (average ischemic area, and partial and approximated ischemic volumes) were also obtained from the ischemic groups. RESULTS: The animal homeostasis parameters remained within acceptable limits for this type of experiment. Regarding the myelinated areas (blue) there was no significant difference between groups C vs. S (p=0,39, Mann-Whitney-Wilcoxon), IC vs. IH3 (p=0,85, Mann-Whitney-Wilcoxon), and IH1 vs. IH2 (p=0,63, Mann-Whitney-Wilcoxon), and there was statistical difference between groups C vs. IC (p=0,0001, Mann-Whitney-Wilcoxon), IC vs. IH1 (p=0,01, Mann-Whitney-Wilcoxon), and IC vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). Regarding the neuronal bodies areas (red) there was no significant difference between groups C vs. S (p=0,48, Mann-Whitney-Wilcoxon), IC vs. IH3 (p=0,27, Mann-Whitney-Wilcoxon), and IH1 vs. IH2 (p=0,68, Mann-Whitney-Wilcoxon), and there was significant difference between C vs. IC groups (p=0,0001, Mann-Whitney-Wilcoxon), IC vs. IH1 (p=0,009, Mann-Whitney-Wilcoxon), and IC vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). Statistical analysis of average ischemic areas, and partial and approximated volumes of ischemic regions showed no significant difference between groups IC vs. IH3 (p=0,57, Mann-Whitney-Wilcoxon), and IH1 vs. IH2 (p=0,79, Mann-Whitney-Wilcoxon), and showed statistical difference between groups IC vs. iH1 (p = 0,0001, Mann-Whitney-Wilcoxon), and IC vs. IH2 (p = 0,0011, Mann-Whitney-Wilcoxon). CONCLUSIONS: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.
26
Silva, de Carvalho Tayana [Verfasser] y Dirk [Akademischer Betreuer] Hermann. "Effects of dietary restriction on ischemic injury, brain remodeling and neuroplasticity after focal cerebral ischemia in mice / Tayana Silva de Carvalho ; Betreuer: Dirk Hermann". Duisburg, 2020. http://d-nb.info/1210861496/34.
27
Onetti, Vilalta Yara. "Influencia del peroxinitrito en los cambios vasculares observados tras la isquemia cerebral focal en rata". Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/394053.
Resumen
Evidencias experimentales demuestran que tras un episodio transitorio de isquemia cerebral focal se inducen cambios estructurales, mecánicos y miogénicos en la pared de las arterias cerebrales, así como un aumento en la producción de peroxinitrito, tanto en los vasos sanguíneos como en el parénquima cerebral. Todas estas alteraciones se han asociado con la expansión del daño cerebral. El peroxinitrito es una especie oxidante/nitrante que, debido a su elevada capacidad de modificar proteínas, puede deteriorar diferentes tejidos, incluido el cerebro. De acuerdo con ello, la presente tesis doctoral hemos hipotetizado que el peroxinitrito es un factor clave implicado en las alteraciones de la arteria cerebral media y del daño cerebral que se observan tras episodios de isquemia-reperfusión. El ácido úrico es un potente antioxidante endógeno que supone las 2/3 partes del poder antioxidante del plasma en humanos, y que tras su administración exógena ha mostrado efectos protectores alentadores en la isquemia. Sin embargo, hasta la fecha, únicamente un estudio ha mostrado una reducción del volumen de infarto cerebral y del daño neurológico después del tratamiento con ácido úrico administrado en un plazo clínicamente relevante. Por otro lado, en estudios previos, el desarrollo de hiperemia reactiva durante el periodo de reperfusión después de un episodio de isquemia cerebral se asoció a un mayor volumen de infarto y déficit neurológico. En la presente tesis confirmamos que las ratas hiperémicas sufren infartos más severos que las que no presentan hiperemia, y que el ácido úrico administrado a los 135 min después de la oclusión de la arteria cerebral media es capaz de atenuar dicho infarto y el daño neurológico asociado. Por lo tanto, demostramos que el ácido úrico administrado exógenamente es altamente efectivo en ratas que presentan signos de hiperemia durante la reperfusión, es decir, en aquellas ratas que padecen un mayor daño cerebral. Además, mostramos que la vasorrelajación inducida por SLIGRL, agonista de los receptores PAR2, en arteria cerebral media precontraída con U46619, análogo estable del TXA2 y agonista de los receptores TP, es mayor en ratas isquémicas que en sham (control). También demostramos que este incremento de la relajación tras la isquemia-referfusión podría estar relacionado con la incapacidad del U46619 para bloquear la relajación mediada por los canales SKCa endoteliales. El mecanismo subyacente a esta observación implicaría un aumento de la acumulación de peroxinitrito y la consiguiente disrupción de la F-actina endotelial, que limitaría la capacidad del U46619 para inhibir la función de los canales SKCa, facilitando así la relajación por EDH tras un episodio de isquemia-referfusión. En conjunto, los resultados obtenidos en el presente estudio muestran que, tras la isquemia-referfusión, el peroxinitrito, mediante su actividad oxidante/nitrosilante, participa en las alteraciones estructurales, mecánicas y vasodilatadoras que se observan en la arteria cerebral media tras un episodio de I/R. Estos hallazgos ayudan a comprender la fisiopatología del ictus isquémico, a la vez que refuerzan el potencial terapéutico de los compuestos antioxidantes con capacidad de neutralizar la acción del peroxinitrito.Experimental evidence shows that, after a transient episode of focal cerebral ischemia, structural, mechanical and myogenic changes in the wall of the cerebral arteries, as well as an increased production of peroxynitrite, are induced in both blood vessels and brain parenchyma. All these alterations have been associated with the expansion of brain damage. Peroxynitrite is an oxidizing/nitriding specie that due to its high capacity to modify proteins, can deteriorate different tissues, including the brain. Accordingly, in this thesis we hypothesized that peroxynitrite is a key factor involved in the alterations of the middle cerebral artery and brain damage observed after episodes of ischemia-reperfusion. Uric acid is a powerful antioxidant endogenous that represents 2/3 of plasma antioxidant in humans and that after exogenous administration has shown promising protective effects in ischemia. However, to date, only one study has shown a reduction in brain infarct volume and neurological damage after treatment with uric acid administered within clinically relevant time. Furthermore, in previous studies, the development of reactive hyperemia during the reperfusion period after a cerebral ischemic episode was associated with increased infarct volume and neurological deficit. In this thesis we confirm that the hyperemic rats suffer more severe infarcts than those ones that don’t experiment hyperemia, and uric acid administered to 135 min after occlusion of the middle cerebral artery is able to attenuate said infarction and associated neurological damage. Therefore, we show that exogenously administered uric acid is highly effective in rats signs of hyperemia during reperfusion, namely, in those rats having higher brain damage. Moreover, we show that vasorelaxation induced by SLIGRL, PAR2 receptor agonist, in middle cerebral artery precontracted with U46619, stable analog of TXA2 and TP receptors agonist, is higher in ischemic rats than in controls (sham). Furthermore, we demonstrate that this increase in relaxation after ischemia-reperfusion may be related to the inability of U46619 to block endothelial relaxation mediated by SKCa channels. The mechanism underlying this observation involve increased accumulation peroxynitrite and consequent disruption of F-actin endothelial, which limit the ability of U46619 to inhibit the function of SKCa channels, thus facilitating the relaxation after an episode of ischemia-reperfusion. Overall, the results obtained in this study show that, after ischemia-reperfusion, the peroxynitrite participates in the structural, mechanical and vasodilator alterations observed in the middle cerebral artery. These findings help to understand the pathophysiology of ischemic stroke, while reinforcing the therapeutic potential of antioxidant compounds capable of neutralizing the action of peroxynitrite.
28
Ota, Tsuyoshi. "Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats". Kyoto University, 2006. http://hdl.handle.net/2433/135643.
29
Carmo, Marta Regina Santos do. "Efeito do PPADS, antagonista do receptor P2, sobre a lesÃo cerebral, comportamento e memÃria de camundongos submetidos à isquemia cerebral focal permanente". Universidade Federal do CearÃ, 2010. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=4924.
Resumen
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgicoApÃs isquemia cerebral, o Trifosfato de Adenosina (ATP) atinge altas concentraÃÃes no espaÃo extracelular e pode atuar como agente tÃxico, que causa degeneraÃÃo celular e morte, mediada atravÃs de receptores P2X e P2Y. No presente estudo, foram investigados os efeitos do PPADS, um antagonista nÃo-seletivo dos receptores P2, sobre o comportamento e dano neuronal apÃs isquemia induzida por oclusÃo permanente da artÃria cerebral mÃdia por eletrocoagulaÃÃo. Os animais receberam PPADS (0,1, 0,5 e 1,0 nmols/1μL) ou fluÃdo cerebroespinhal artificial (FCE) por injeÃÃo intracerebroventricular 10 min antes da isquemia. Os parÃmetros estudados foram funÃÃo sensÃrio-motora, aquisiÃÃo e retenÃÃo de memÃria, Ãrea de infarto cerebral e atividade da MPO, como marcador para infiltraÃÃo granulocÃtica. ApÃs isquemia, verificou-se atravÃs de avaliaÃÃo neurolÃgica, uma diminuiÃÃo significante do desempenho motor e funÃÃo sensorial dos animais. A percentagem da Ãrea de infarto nos animais falso-operados foi significantemente menor que naqueles submetidos à isquemia (FO: 0,89  0,18%; FO + PPADS 1,0: 1,18  0,1%; ISQ: 9,06  1,2%; ISQ + PPADS 0,5: 2,2  0,32%; ISQ + PPADS 1,0: 1,86  0, 18%). Foi observado ainda um aumento da atividade exploratÃria vertical (n de Rearings) nos animais tratados com PPADS quando comparados aos animais do grupo isquemiado (ISQ: 9,5  1,8; ISQ + PPADS 0,5: 26,9  2,9; ISQ + PPADS 1,0: 20,6  3,7; Kruskall-Wallis, p<0.05). O tratamento com PPADS melhorou de forma significante os dÃficits na memÃria operacional induzidos pela isquemia, avaliado no teste do Labirinto em Y (FO: 73,8  1,9%; ISQ: 56,7  2,9%; ISQ + PPADS 0,5: 76,7  3,2%; ISQ + PPADS 1,0: 72,6  4,0%). Um resultado semelhante foi observado na memÃria aversiva (teste da esquiva passiva) no qual o PPADS melhorou a aquisiÃÃo de memÃria de curta duraÃÃo. Os animais isquemiados demonstraram um aumento nos nÃveis de MPO no estriado (FO: 3,6  0,63; ISQ: 16,24  4,86) e cÃrtex temporal (FO: 6,16  1,23; ISQ: 22,33  4,98), e o tratamento com PPADS (1,0 nmols/1μL) reverteu significantemente esse efeito (ISQ + PPADS â estriado: 6,13  0,65; cÃrtex: 6,28  0,38). Os resultados demonstram o envolvimento dos receptores P2 na fisiopatologia da isquemia cerebral. A inibiÃÃo dos receptores P2 pelo PPADS mostrou um significante efeito neuroprotetor sobre o dano neuronal, comportamento motor e memÃria apÃs isquemia e indicam que este efeito pode estar relacionado pelo menos em parte a uma atividade antiinflamatÃria deste composto.
30
Fonteles, Analu AragÃo. "Efeito Neuroprotetor do Ãcido RosmarÃnico no Dano Neuronal, DÃficit de MemÃria e Resposta InflamatÃria de Camundongos Submetidos à Isquemia Cerebral Focal Permanente". Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=10790.
Resumen
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorO acidente vascular cerebral (AVC) resulta da interrupÃÃo aguda do fluxo sanguÃneo aos tecidos cerebrais, resultando no decrÃscimo de oxigÃnio e glicose para os tecidos e consequentemente em perda rÃpida da funÃÃo neurolÃgica. à a segunda principal causa de morte no mundo e uma das principais causas de incapacidade fÃsica segundo dados da OrganizaÃÃo Mundial de SaÃde. No Brasil ocorrem cerca de 100 mil Ãbitos por ano devido ao AVC. O AVC pode ser dividido em dois tipos, isquÃmico, quando ocorre a interrupÃÃo do fluxo sanguÃneo devido à obstruÃÃo por um trombo ou Ãmbolo, e hemorrÃgico, quando ocorre rompimento de uma artÃria cerebral. Aproximadamente, 80% dos casos de AVC sÃo devidos a isquemia cerebral. A falta de glicose e oxigÃnio no tecido neuronal promove uma deficiÃncia da sÃntese de ATP que resulta em um colapso nos mecanismos dependentes de energia precipitando uma cascata de eventos que envolvem estresse oxidativo, inflamaÃÃo e morte neuronal. O Ãcido rosmarÃnico à um polifenol encontrado nas plantas da famÃlia das Laminaceae que possui atividade anti-inflamatÃria, antioxidante e anti-apoptÃtica jà descritas. Apesar de muitos estudos buscarem drogas neuroprotetoras para o AVC isquÃmico, poucos se mostraram realmente efetivos. Assim se torna evidente a necessidade de estudar os polifenÃis que possam vir a ser uma estratÃgia terapÃutica no tratamento do AVC. O objetivo deste trabalho foi estudar os efeitos do Ãcido rosmarÃnico sobre o dano neuronal, dÃficits de memÃria e resposta infamatÃria de camundongos submetidos à isquemia cerebral focal permanente experimental induzida por oclusÃo da artÃria cerebral mÃdia. O modelo de isquemia cerebral focal permanente foi comprovado atravÃs do aumento significativo nas percentagens das Ãreas de infarto, atravÃs da coloraÃÃo com TTC, nos animais isquemiados. O Ãcido rosmarÃnico diminuiu a de Ãrea de lesÃo isquÃmica nos animais isquemiados nas doses de 1, 10 e 20 mg/kg. A ICF produziu dÃficits sensÃrio-motor significativos na avaliaÃÃo neurolÃgica. O Ãcido rosmarÃnico preveniu significativamente o dÃficits sensÃrio-motor nas doses de 1, 10 e 20 mg/kg. O modelo utilizado nÃo apresentou alteraÃÃes na atividade locomotora dos animais. O modelo de isquemia produziu dÃficits de memÃria de trabalho, memÃria episÃdica, memÃria espacial e de memÃria aversiva. O tratamento com o Ãcido rosmarÃnico na dose de 20 mg/kg preveniu os dÃficits na memÃria de trabalho, memÃria episÃdica e memÃria espacial. A ICF provocou aumento da mieloperoxidase (CÃtex temporal: FO: 0,85Â0,42; FO + AR 20: 1,23Â0,71; ICF: 5,65Â1,4; Corpo estriado: FO: 0,60Â0,29; FO + AR 20: 0,75Â0,36; ICF: 1,34Â0,33) e ativaÃÃo de astrÃcitos no cÃrtex temporal e no corpo estriado (FO: 109,2 4,3; ICF: 152,9 8,8). O Ãcido rosmarÃnico na dose de 20 mg/kg preveniu o aumento da MPO no cÃrtex temporal (ICF + AR 20: 3,50Â0,87) e a astrogliose no cÃrtex temporal e corpo estriado (ICF + AR 20: 124,4Â6,2). Os resultados do presente estudo sugerem que o Ãcido rosmarÃnico possui atividade neuroprotetora provavelmente devido a sua aÃÃo anti-inflamatÃria.
Ischemic cerebrovascular accident results from reduced blood supply to brain tissue, resulting in deprivation of glucose and oxygen characterized by rapid loss of neurological function. Stroke itâs the second leading cause of death and the first cause of disability worldwide. In Brazil occurs one hundred cases of death a year. The stroke can be divided into two types: ischemic, that results of a obstruction in the blood flux, and hemorrhagic, that results of a ruption of blood vessels. Aproximately 80% of strokes are due to cerebral ischemia. Glucose and oxygen deprivation leads to a cascade of events, including oxidative stress and inflammation, that culminate in neuronal death. Rosmarinic acid is a polifenol found in the Laminaceae family with known anti-inflammatory, antioxidant and antiapoptotic activities. Although many studies seek neuroprotective drugs for ischemic stroke, few have proved really effective. Thus it becomes evident the need to study the polyphenols that may be a therapeutic strategy in the treatment of stroke. The aim of this work was study the effect of rosmarÃnico acid in the neuronal damage, memory deficits and inflammatory response in mice subjected to experimental model of focal cerebral brain ischemia by occlusion of middle cerebral artery (oMCA). The model of cerebral ischemia was proven by the significant increase in the percentage of infarct area by TTC staining in ischemic animals. The rosmarÃnico acid (1, 10 e 20 mg/kg) significantly decreased the percentage of lesion area caused by ischemia. oMCA produced significant sensorimotor dÃficits in neurological evaluation. The rosmarÃnico acid (1, 10 e 20 mg/kg) prevented the sensorimotor deficits. The MCAo showed no changes in locomotor activity in animals. The MCAo produced deficits in operational memory, episodic memory, spatial memory and aversive memory. The treatment with rosmarinic acid (20 mg/kg) prevented memory deficits. The MCAo increased the MPO level (temporal cÃrtex: FO: 0,85Â0,42; FO + AR 20: 1,23Â0,71; ICF: 5,65Â1,4; striatum: FO: 0,60Â0,29; FO + AR 20: 0,75Â0,36; ICF: 1,34Â0,33) and the astroglioses (FO: 109,2Â 4,3; ICF: 152,9Â 8,8) in the temporal cortex and striatum. The treatment with rosmarinic acid prevented MPO increase (ICF + AR 20: 3,50Â0,87) and activation of astrÃcitos (ICF + AR 20: 124,4Â6,2). The MCAo induced an decrease in synaptofisin expression and rosmarÃnico acid prevented (FO: 100,0Â1,9; ICF: 77,1Â5,7; ICF + AR 20: 88,6Â4,0). The results of this study suggests that rosmarinic acid has neuroprotective activity probably due to its antinflammatory action.
31
Heydenreich, Nadine Verfasser], Guido [Gutachter] Stoll y Thomas [Gutachter] [Dandekar. "Studies on the contact-kinin system and macrophage activation in experimental focal cerebral ischemia / Nadine Heydenreich. Gutachter: Guido Stoll ; Thomas Dandekar". Würzburg : Universität Würzburg, 2013. http://d-nb.info/1108780695/34.
32
Heydenreich, Nadine [Verfasser], Guido Gutachter] Stoll y Thomas [Gutachter] [Dandekar. "Studies on the contact-kinin system and macrophage activation in experimental focal cerebral ischemia / Nadine Heydenreich. Gutachter: Guido Stoll ; Thomas Dandekar". Würzburg : Universität Würzburg, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-94534.
33
Rabiller, Gratianne. "Contribution of hippocampal diaschisis to the memory deficits associated with focal cerebral ischemia in the rat : converging behavioral, electrophysiological and functional evidence". Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0461/document.
Resumen
Les mécanismes impliqués dans les troubles cognitifs induits à la suite d’une ischémie cérébrale (IC) demeurent mal compris. En plus du cœur ischémique nécrosé et de la zone de pénombre entourant cette lésion, certaines régions éloignées de la zone ischémique peuvent être fonctionnellement affectées, un phénomène connu sous le nom de «diaschisis». Sachant qu’il existe de fortes interactions fonctionnelles entre l’hippocampe (HPC) et le cortex lors des processus mnésiques, nous avons émis la possibilité que les troubles mnésiques survenant après une IC focale qui préserve l’intégrité de l’HPC, auraient pour origine une perturbation de la connectivité cortico-hippocampique conduisant à un hypofonctionnement hippocampique induit par le phénomène de diaschisis. Afin d’éprouver cette hypothèse, nous avons utilisé le modèle d’occlusion permanente de l'artère cérébrale moyenne chez le rat (OPACM) qui reproduit l’ischémie cérébrale focale humaine. Dans ce modèle, le cortex somato-sensoriel (SS) est endommagé unilatéralement alors que l’intégrité de l’HPC est préservé. Les rats OPACM ont montré une diminution de l’expression du gène c-fos dans l’HPC lors de l'exploration d'un nouvel environnement, indiquant une hypoactivation neuronale. Les rats OPACM ont également présenté une perturbation des mémoires olfactive associative et spatiale lors des tests de transmission sociale de préférence alimentaire (TSPA) et du Barnes maze, respectivement. Afin de confirmer que l’hypofonctionnement hippocampique induit par l’IC résultait d’une réduction des afférences corticales («déactivation») provenant du cortex endommagé, nous avons réalisé des inactivations pharmacologiques spécifiques du cortex SS et ou de l’HPC par injection de lidocaïne ou de CNQX. Ces injections ont induit une hypoactivation hippocampique (réduction du nombre de noyaux Fos-positifs) associée à une perturbation mnésique dans le test de TSPA. L'activité hippocampique chez des rats anesthésiés pendant l’IC ou deux semaines après, ainsi que lors de l’inactivation pharmacologique du cortex SS, a également été examinée par une approche électrophysiologique. Les résultats ont montré une altération de la fréquence d’apparition des «sharp-wave ripples» hippocampiques et révélé une instabilité de la fréquence thêta hippocampique lors de la reperfusion ou deux semaines après IC, ainsi que lors de l’inactivation corticale, suggérant une altération de la dynamique d’interaction entre l’HPC et le cortex. Pris dans leur ensemble, ces résultats identifient le phénomène de diaschisis hippocampique comme un mécanisme crucial impliqué dans l’hypofonctionnement hippocampique et les déficits mnésiques observés après une ICThe cognitive consequences and the underlying mechanisms leading to cognitive impairments after cerebrovascular occlusive diseases are still unclear. In addition to the infarct zone that suffer the deadly consequence of ischemic stroke, the penumbra surrounding the lesion site and some brain regions more remote to the ischemic areas can be functionally affected by the insult. This phenomenon is referred to as diaschisis. In light of the importance of interactions between hippocampus and cortex during memory processing, we hypothesized that the cognitive impairments observed following focal ischemia could occur in the absence of direct hippocampal insult, possibly via impaired connectivity within cortico-hippocampal networks leading to diaschisis-induced hypofunctioning in specific hippocampal subregions. To examine this possibility, we used the distal middle cerebral artery occlusion (dMCAO) ischemic model in rats which induces restricted cortical infarct in the somatosensory (SS) cortex in the absence of direct hippocampal injury. dMCAO rats exhibited reduced expression of the activity-dependent gene c-fos in the hippocampus when exploring a novel environment, indicating neuronal hypoactivation. Ischemic rats also showed impaired associative olfactory and spatial memory when tested in the social transmission of food preference (STFP) task and the Barnes maze test, respectively. To confirm that the ischemic-induced hippocampal hypofunctioning resulted from reduced afferent inputs (i.e. deactivation) originating in the damaged cortex, we performed region-specific pharmacological inactivation of SS and/or HPC using lidocaine or CNQX. Fos imaging revealed that these treatments induced hippocampal hypoactivation and impaired memory performance as measured in the STFP task. We additionally performed electrophysiological recordings of hippocampal activity in anesthetized rats during acute stroke and two weeks later or after SS cortex inactivation. We found an alteration in the occurrence of sharp-wave ripples associated with instability of theta frequency during reperfusion after stroke and SS cortex inactivation, suggesting an alteration in the dynamics of hippocampal-cortical interactions. Taken collectively, these findings identify hippocampal diaschisis as a crucial mechanism for mediating stroke-induced hippocampal hypofunction and associated memory deficits
34
Craft, Tara K. S. "Psychological determinants of stroke outcome in mice". Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1150315601.
35
Wang, Yachao [Verfasser] y Dirk [Akademischer Betreuer] Hermann. "Post-acute delivery of NMDA or GABAA α5 receptor antagonists promotes neurological recovery and peri-infarct brain remodeling after transient focal cerebral ischemia in mice / Yachao Wang ; Betreuer: Dirk Hermann". Duisburg, 2019. http://d-nb.info/1191692272/34.
36
Wehner, Tim. "Einwanderung und Differenzierung von hämatogenen Zellen zu Mikroglia im adulten Zentralnervensystem". Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2004. http://dx.doi.org/10.18452/15004.
Resumen
Zur langfristigen Markierung von hämatogenen Zellen wurde Knochenmark mit dem Gen für das grüne fluoreszierende Protein (GFP) transduziert und in bestrahlte Empfängermäuse transplantiert. Die GFP-Expression im peripheren Blut dieser Tiere war über den untersuchten Zeitraum von vier Monaten stabil. Die Hirne der Empfängertiere wurden zu den Zeitpunkten zwei, vier, acht und fünfzehn Wochen nach Knochenmarktransplantation auf die Präsenz von GFP-exprimierenden Zellen untersucht. Es fand sich eine im Zeitverlauf zunehmende Einwanderung und Differenzierung von GFP-exprimierenden hämatogenen Zellen zu ramifizierten Mikrogliazellen in der grauen und weißen Substanz. Nach vier Monaten stammten bis zu ein Viertel aller regionalen Mikrogliazellen aus dem transplantierten Knochenmark. Nach fokaler cerebraler Ischämie wanderten deutlich mehr GFP-positive Zellen aus dem Blut in das ischämische Areal ein und differenzierten zu ramifizierten Mikrogliazellen. Diese Ergebnisse implizieren einen Weg für den Transfer des humanen Immunodefizienzvirus in das Zentralnervensystem und offerieren einen nichtinvasiven Weg, genetisch manipulierte Zellen in das adulte Hirnparenchym einzuschleusen.In order to stably label hematogenous cells, bone marrow was transduced with the gene for the green fluorescent protein (GFP) and transplanted into irradiated recipient mice. The GFP- expression in peripheral blood cells of these animals was stable within the examined time frame of four months. Brains of recipient animals were examined for the presence of GFP- expressing cells at two, four, eight and fifteen weeks after bone marrow transplantation. An increasing migration and differentiation of hematogenous GFP-expressing cells into ramified parenchymal microglia within the white and grey matter was found. After four months, up to quarter of regional microglia were bone-marrow derived. Following focal cerebral ischemia, an increased influx of GFP-positive blood-borne cells differentiating into ramified microglia was observed. These results imply a route for the human immunodeficiency virus into the central nervous system, and they offer a noninvasive approach for the transfer of genetically manipulated cells into the adult brain parenchyma.
37
BOUTIN, HERVE. "Evolution des recepteurs opioidergiques , et cerebraux apres ischemie cerebrale focale permanente ou transitoire chez la souris". Caen, 1998. http://www.theses.fr/1998CAEN2017.
Resumen
Les traitements de l'ischemie cerebrale, l'accident vasculaire cerebral le plus frequent chez l'homme, sont encore peu nombreux. Le role neuromodulateur du systeme opioidergique sur de nombreux autres systemes de neurotransmission et des etudes de neuroprotection ont clairement demontre l'implication du systeme opioidergique dans les processus ischemiques, mais peu d'etudes visant a etudier l'evolution du systeme opioidergique apres ischemie cerebrale focale ont ete menees a bien. Le but de la presente etude etait donc de determiner l'evolution des recepteurs opioides durant la phase aigue, subaigue et chronique apres occlusion permanente ou transitoire de l'artere cerebrale moyenne (oacm) chez la souris. Nous avons ainsi mis en evidence une diminution precoce (6h) des densites en recepteurs et dans les aires corticales infarcies et periinfarcies (penombre) apres ischemie permanente, qui est correlee aux dommages histologiques survenant a 24h post-oacm apres ischemie transitoire. Parallelement, les densites en recepteurs sont preserves pendant la phase aigue de l'ischemie, et ne sont significativement diminues que 12h a 24h apres ischemie permanente ; de plus, les recepteurs ne sont alteres que dans quelques aires corticales peri-infarcies apres ischemie transitoire. Dans des structures cerebrales sous-corticales non-infarcies (exofocales) (thalamus, substantia nigra, striatum), le nombre de recepteurs opioides est egalement altere. Les alterations precoce du nombre de recepteurs et durant la phase aigue de l'ischemie, suggerent l'utilisation des recepteurs opioides comme marqueurs 1/predictifs de l'atteinte neuronale survenant dans le tissus infarcis et peri-infarcis, et 2/d'atteintes fonctionnelles dans les regions exofocales. Parallelement, la preservation des recepteurs suggere une utilisation possible de ces recepteurs comme cible d'agents neuroprotecteurs avec une fenetre d'opportunite therapeutique large (>6h post-ischemie).
38
VandenBerg, Penny M. y University of Lethbridge Faculty of Arts and Science. "Associative diaschisis and skilled rehabilitation-induced behavioral recovery following focal ischemic infact". Thesis, Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 2002, 2002. http://hdl.handle.net/10133/207.
Resumen
The time course of peri-infarct diaschisis following a focal ischemic infarct and the effects of delayed rehabilitation on behavioral and functional recovery were examined. Intracortical microstimulation (ICMS) was used to derive topographical maps of forelimb representations within the rat motor cortex and ischemia was induced via bipolar coagulation of surface vasculature. At one hour there was a dramatic expansion of reprentations in control but not ischemic animals. A significant loss of forelimb representations within peri-infarct dysfunction indicates the need for immediate administration of therapeutic interventions following an ischemic event. These results indicate that the timing of rehabilitation does not effect functional and behavioral recovery but does support the need for rehabilitative interventions of facilitate these types of recovery.132 leaves : ill. ; 28 cm.
39
von, Geymüller Teresa. "Einfluss einer autologen Knochenmarkzelltherapie auf reaktive Astrogliose und Glukosetransporter-1-Expression in grauer und weißer Substanz des Großhirns nach fokaler zerebraler Ischämie beim Schaf". Doctoral thesis, Universitätsbibliothek Leipzig, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-98722.
Resumen
Ziele der hier vorliegenden Arbeit waren eine immunhistochemische Analyse von GFAP (‚glial fibrillary acidic protein’) und GLUT-1 (Glukosetransporter-1) nach fokaler zerebraler Ischämie sowie deren mögliche Beeinflussung durch eine intravenöse Transplantation autologer mononukleärer Knochenmarkzellen (mKMZ) im Schafmodell. Eine differenzierte Analyse der Zielstrukturen in grauer und weißer Substanz (GS bzw. WS) sollte Aufschluss über eventuell unterschiedliche Reaktionsmuster liefern.
Das Gehirnmaterial von zehn Tieren der bereits 2006/2007 stattgefundenen Studie, welche mit PET und MRT-Untersuchungen sowie der Durchführung von Verhaltenstests einherging, wurde retrospektiv im Rahmen der vorliegenden Arbeit untersucht. Je fünf gehörten zu einer Kontroll- bzw. Therapiegruppe (KG bzw. TG). Bei allen Versuchstieren wurde durch die permanente Okklusion der linken mittleren Zerebralarterie (pMCAO) eine fokale zerebrale Ischämie im Bereich des Neokortex hervorgerufen. Die Tiere der Therapiegruppe erhielten 24 Stunden nach dem Eingriff eine Transplantation autologer mKMZ (4x106/kg KGew). Nach sieben Wochen wurden die Versuchstiere getötet, ihre Schädel perfundiert und ihre Gehirne fixiert. Eine Lamelle der Gehirne wurde für die anschließende histologische Untersuchung in 30% Saccharose konserviert.
Nach der Etablierung der Antikörper GFAP und GLUT-1 wurden vier Regionen der Gehirn-lamellen immunhistochemisch markiert und abschließend qualitativ und quantitativ analysiert. Die Regionen I (infarktnah) und III (infarktfern) lagen in der ipsilateralen Hemisphäre, die Regionen II (korrespondierend zu Region I) und IV (korrespondierend zu Region III) in der kontralateralen Hemisphäre. Durch den höheren Substanzverlust an Gehirnmasse in der ipsi-lateralen Hemisphäre der KG, wurden in dieser Tiergruppe die Regionen III und IV nicht ausgewertet. Vor der Analyse sind die physiologischen Markierungsmuster der vier Regionen in grauer und weißer Substanz an zwei gesunden Tieren (Prozesskontrolle) aufgezeigt worden. Durch die elektronenmikroskopische Untersuchung von Präparaten und anhand von GFAP/GLUT-1 doppelmarkierten Präparaten konnte festgestellt werden, dass die Astrozytenendfüßchen durch den hier verwendeten GLUT-1 Antikörper nicht markiert wur-den, sondern dass alleinig die gefäßständige, 55 kDa schwere Isoform detektiert worden ist. Die fokale zerebrale Ischämie führte in beiden Gruppen zu einer hochgradigen reaktiven Astrogliose mit Ausprägung einer Glianarbe in Region I. Protoplasmatische Astrozyten der grauen und fibrilläre Astrozyten der weißen Substanz zeigten hypertrophe Veränderungen. Die reaktive Astrogliose von Region I spiegelte sich in einer erhöhten GFAP-Dichte wider (p<0,05 in der Therapiegruppe). Region III hatte die gleiche GFAP-Dichte wie die Regionen II und IV. Der direkte Vergleich zwischen den Regionen I der beiden Gruppen zeigte Veränderungen der GFAP-Dichte durch die Zelltherapie auf: In der GS der Therapiegruppe lag eine geringere GFAP-Dichte vor, in der WS eine höhere (≠ p<0,05; GS und WS).
Die Ergebnisse der GLUT-1-Analyse sind denen der GFAP-Analyse sehr ähnlich. Durch den Schlaganfall ist es zu einer erhöhten GLUT-1-Expression in GS und WS (p<0,05 WS) von Region I der Kontrollgruppe gekommen. Auch in Region I der Therapiegruppe konnten er-höhte GLUT-1-Dichten in GS und WS (p<0,05 WS) detektiert werden, zusätzlich dazu lag in der GS von Region III der Therapiegruppe eine erhöhte GLUT-1-Dichte vor (p<0,05). Der Vergleich zwischen beiden Gruppen zeigte Veränderungen durch die Therapie für die Regio-nen I und II auf. Die GLUT-1-Dichte der WS war in beiden Regionen in der TG erhöht (p<0,05), die GS von Region I zeigte in der Therapiegruppe eine geringere GLUT-1-Dichte.
Ein Schlaganfall führt zu einer Erhöhung der GFAP sowie GLUT-1-Dichten in WS und GS im infarktnahen Gebiet. Durch die Transplantation von 4x106 autologen mononukleären Knochenmarkzellen pro kg KGew 24 Stunden nach dem Schlaganfall können diese Strukturen in ihren Expressionsmustern beeinflusst werden, dabei reagieren graue und weiße Substanz unterschiedlich: Die GS mit einer Verringerung, die WS mit einer Erhöhung der GFAP- bzw. GLUT-1-Dichte (p<0,05 WS, GLUT-1). Die Funktionskreisläufe in infarktfernen Regionen sind sieben Wochen nach dem Schlaganfall auf Astrozytenebene normalisiert (vgl. Region III). Die erhöhte GLUT-1-Dichte (p<0,05) in der GS der infarktfernen Region ist möglicherweise mit einem erhöhten Glukosemetabolismus in Verbindung zu setzen. Dies kann jedoch erst durch die Auswertung der FDG-PET-Daten beantwortet werden. Ob die durch Transplantation autologer mKMZ festgestellten Veränderungen der GFAP- und GLUT-1-Dichte in der Therapiegruppe zusätzlich mit einer verbesserten motorischen Leistung der Tiere einhergingen, wird erst durch die Analyse der Daten aus den Verhaltenstests festgestellt werden können.
40
Fernandes, Francisco Diego Pinheiro. "Study of the neuroprotective effect of caffeic acid in mice after permanent focal cerebral ischemias". Universidade Federal do CearÃ, 2014. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=12024.
Resumen
FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgicoBrain ischemia results from the acute interruption of blood flow to the brain tissue vascular accident resulting in the decrease of glucose and oxygen to the tissues and consequently to a rapid loss of neurological function. It is the second leading cause of death worldwide and a major cause of disability according to the World Health Organization. Brain stroke pathophysiology involves a complex cascade of events such as inflammation and oxidative stress that lead to neuronal loss and cognitive deficits. Caffeic acid is a natural phenolic compound with antioxidant and anti-inflammatory properties. To evaluate the neuroprotective efficacy of this compound in mice subjected to a permanent middle cerebral artery occlusion (pMCAO), animals were pre-and post-treated with caffeic acid 2, 20 and 60mg/kg, i.p. during 24, 48, 72, 96 or 120h after ischemia. Animals were evaluated at 24 h after the pMCAO for brain infarction and neurological deficit score. At 72 h after the occlusion, animals were evaluated for locomotor activity, working memory and short aversive memory; late aversive memory was evaluated 24 h after the evaluation of short aversive memory. Finally, at 120 h after the event, spatial memory and the expression levels of synaptophysin, SNAP 25 and caspase 3 were evaluated. The treatment with caffeic acid reduced the infarcted area and improved neurological deficit scores. There was no difference in locomotor activity between groups. The working, spatial and late aversive memory deficits were improved by caffeic acid. Furthermore, western blotting data showed that the expression of synaptophysin which correlates with synaptic formation and function, decreased after ischemic insult, caffeic acid inhibited the reduction of synaptophysin expression. The treatment also decreased caspase 3 expression. These results suggest that caffeic acid possesses neuroprotective and anti-dementia properties, at least in part, by preventing the loss of neural cells and synapses in ischemic brain injury.
EFEITO NEUROPROTETOR DO ÃCIDO CAFEICO EM CAMUNDONGOS SUBMETIDOS à ISQUEMIA CEREBRAL FOCAL PERMANENTE. O acidente vascular cerebral (AVC) resulta da interrupÃÃo aguda do fluxo sanguÃneo aos tecidos cerebrais, resultando no decrÃscimo de oxigÃnio e glicose para os tecidos e consequentemente em perda rÃpida da funÃÃo neurolÃgica. à a segunda principal causa de morte no mundo e uma das principais causas de incapacidade fÃsica segundo dados da OrganizaÃÃo mundial de SaÃde. A fisiopatologia do AVC isquÃmico envolve uma complexa cascata de eventos como a inflamaÃÃo e o estresse oxidativo que levarÃo à morte neuronal e dÃficits cognitivos. O Ãcido cafeico à um composto fenÃlico natural com propriedades anti-oxidantes e antiinflamatÃrias. Para avaliar o efeito neuroprotetor deste composto em camundongos submetidos à oclusÃo permanente da artÃria cerebral media, os animais foram prà e pos tratados com Ãcido cafeico nas doses de 2, 20 e 60 mg/kg, i.p., durante 24, 48, 72, 96 ou 120 horas apÃs a isquemia. Os animais foram avaliados 24h apÃs a isquemia para verificar a Ãrea de lesÃo isquÃmica e avaliaÃÃo neurolÃgica. Setenta e duas horas apÃs a oclusÃo, os testes de atividade locomotora, memÃria de trabalho e memÃria aversiva recente foram realizados e a memÃria aversiva tardia realizou-se 24h depois da memÃria recente. Finalmente, 120h apÃs a isquemia, avaliou-se a memÃria espacial e as expressÃes de sinaptofisina, SNAP25 e caspase 3. O tratamento com o Ãcido cafeico reduziu a lesÃo isquemica e melhorou os escores na avaliaÃÃo neurologica. NÃo houve diferenÃa na atividade locomotora entre os grupos. O Ãcido cafeico mostrou proteÃÃo nas memÃrias de trabalho, espacial e aversiva tardia. AlÃm disso, as anÃlises de western blotting mostraram que expressÃo de sinaptofisina, que està relacionada com a funÃÃo e formaÃÃo sinÃptica, diminiu apÃs o insulto isquÃmico e que o acido cafeico inibiu a reduÃÃo da expressÃo de sinaptofisina. Observou-se um aumento na expressÃo de caspase 3 nos animais isquemiados e essa expressÃo foi diminuida pelo tratamento com o Ãcido cafeico. Esses resultados sugerem que as propriedades neuroprotetoras e anti-demencia do Ãcido cafeico possui estÃo relacionadas na prevenÃÃo da perda de celulas neurais e das sinapses no cÃrebro apÃs a lesÃo isquÃmica.
41
Detante, Olivier. "THERAPIE CELLULAIRE PAR CELLULES SOUCHES MESENCHYMATEUSES HUMAINES APRES ISCHEMIE CEREBRALE". Phd thesis, Université de Grenoble, 2010. http://tel.archives-ouvertes.fr/tel-00905941.
Resumen
Les accidents vasculaires cérébraux (AVC) sont la première cause de handicap de l'adulte. Favoriser la plasticité cérébrale post-lésionnelle représente un objectif thérapeutique majeur. Dans ce contexte, la thérapie cellulaire a récemment émergé. Son action, fondée sur la " réparation " du tissu cérébral, a montré un bénéfice sur la récupération fonctionnelle dans des modèles d'ischémie cérébrale. La transposition de ce traitement à l'homme reste à ce jour limitée à des études pilotes. Dans nos travaux précliniques, nous avons montré, après un infarctus cérébral chez le rat, une bonne tolérance et un bénéfice fonctionnel de l'administration intracérébrale (à la phase aiguë) et intraveineuse (à la phase subaiguë) de cellules souches mésenchymateuses humaines (CSMh) de grade clinique. La survie des CSMh greffées (possible durant plusieurs semaines) et leur différenciation en cellules d'intérêt (neurones, astrocytes) sont très faibles et ne peuvent expliquer à elles seules le bénéfice observé. Parmi les mécanismes d'action possibles des CSM (effet neurotrophique, pro-angiogénique, immunomodulation...), nous avons mis en évidence par IRM un effet microvasculaire précoce. Nous avons également montré l'innocuité du marquage des CSMh par microparticules ferriques pour l'IRM cellulaire et la microscopie. Ce marquage cellulaire est utile pour détecter et suivre par IRM des cellules greffées au sein du cerveau (durant au moins 15 jours), mais nous a paru insuffisant dans le cadre d'une injection IV. Pour évaluer la biodistribution des CSMh injectées par voie IV à la phase subaiguë, nous avons effectué une étude par imagerie nucléaire qui a permis d'identifier l'attraction rapide de CSMh vers l'infarctus cérébral. En parallèle, la mise en place d'un essai clinique de phase 2 a été effectuée. Le délai, la voie optimale d'administration ainsi que la source cellulaire à utiliser restent encore controversés. L'optimisation de la thérapie cellulaire nécessite encore le développement de projets de recherche translationnelle associant les études expérimentales et les essais cliniques. C'est dans ces conditions que la thérapie cellulaire pourrait devenir un traitement efficace après un AVC.
42
Berry, Isabelle. "Ischemie cerebrale focale aigue experimentale : apport de l'imagerie et de la spectroscopie par resonnance magnetique (irm/srm)". Toulouse 3, 1989. http://www.theses.fr/1989TOU30080.
Resumen
Etude de la valeur diagnostique et pronostique du couplage imagerie/spectroscopie par resonance magnetique. Ces deux techniques permettent d'etudier l'aspect metabolique et l'aspect hemodynamique de l'ischemie cerebrale
43
Touzani, Omar. "Evolution du metabolisme oxydatif cerebral apres ischemie focale chez le babouin anesthesie : etude en tomographie par emission de positons". Caen, 1996. http://www.theses.fr/1996CAEN2013.
Resumen
Afin de mieux comprendre l'evolution du tissu ischemique vers l'infactus, nous nous sommes interesses principalement dans ce travail a l'evolutivite temporo-spatiale du volume tissulaire hypometabolique et ses caracteristiques physiopathologiques apres induction d'ischemie focale chez le babouin anesthesie, au moyen d'etudes sequentielles en tomographie par emission de positons (tep). Nous avons montre que l'occlusion permanente de l'artere sylvienne induit une extension progressive du volume du tissu severement hypometabolique jusqu'au moins la 24eme heure apres l'ictus. Ceci indique l'existence d'une fenetre d'opportunite therapeutique relativement longue dans laquelle une intervention therapeutique peut etre envisagee. En se basant sur les resultats obtenus chez les babouins soumis a une occlusion permanente de l'artere sylvienne, nous avons examine l'effet de la restauration du debit sanguin cerebral sur le profil evolutif de l'hypometabolisme severe consecutif a une ischemie cerebrale. Ainsi, nous nous sommes attaches a realiser la meme analyse dans un modele d'ischemie temporaire (6 h) chez le babouin anesthesie. Les donnees obtenues dans ce modele, proche de la pathologie rencontree en clinique humaine, montrent que la reperfusion, instituee meme apres 6 h d'occlusion, permet non seulement de prevenir l'extension progressive du volume tissulaire severement hypometabolique, mais aussi de retablir partiellement le metabolisme oxydatif cerebral. Il en resulte une reduction considerable du volume de l'infarctus final. Ces resultats sont en faveur d'un effet benefique de la reperfusion sur le devenir tissulaire apres une occlusion arterielle
44
Loubinoux, Isabelle. "Mise en évidence des potentialités des techniques de RMN "in vivo" pour caractériser la dynamique des évènements métaboliques cérébraux : par spectroscopie 1D et 2D au cours d'une activation cérébrale par imagerie de diffusion et de T2 consécutivement àune ischémie cérébrale". Paris 11, 1995. http://www.theses.fr/1995PA11T024.
45
Plotkine, David. "Rôle de l'apoptose dans la mort cellulaire suivant l'ischémie cérébrale focale chez le raton". Paris 5, 1999. http://www.theses.fr/1999PA05P011.
46
JAMME, ISABELLE. "Modulation d'activite et d'expression de la na#+, k#+-atpase et de ses isoformes apres ischemie cerebrale focale chez la souris". Caen, 1997. http://www.theses.fr/1997CAEN2028.
Resumen
Afin de determiner le role des alterations de la na#+, k#+-atpase au cours de l'ischemie cerebrale, nous avons etudie, a partir d'un modele d'ischemie cerebrale focale chez la souris, les modulations d'activite et d'expression de l'enzyme et de ses isoformes. Ces differentes isoformes (1, 2, 3) sont caracterisees par leur affinite a l'ouabaine. Nos etudes ont ete realisees in vitro a partir de microsomes corticaux de cerveau de souris et ex vivo par autoradiographie quantitative a l'ouabaine sur coupes de cerveau. A partir de l'etude realisee in vitro, nous avons montre 1/une diminution d'activite precoce de la na#+, k#+-atpase apres ischemie 2/une disparition de l'un des trois sites de liaison de l'ouabaine 3/une augmentation d'affinite en fonction de la duree de l'ischemie, des deux sites de liaison de l'ouabaine restants et 4/une diminution de l'activite specifique du site de plus haute affinite a l'ouabaine detecte apres ischemie. Par ailleurs, aucune modification d'expression des arnmessagers et des proteines des isoformes et n'a ete decelee. En parallele, des changements de densite des sites de liaison de l'ouabaine determinees pour les isoformes 2 et 3 sont observes ex vivo, aussi bien dans des structures lesees que dans certaines regions a distance du foyer ischemique. Des diminutions precoces de densite de sites de liaison sont observees dans les regions lesees. Un retour a la normale est quasi toujours observe pour les sites de haute affinite a l'ouabaine (isoformes 2) tandis que des pertes de densite de sites de liaison subsistent pour les sites de tres haute affinite a l'ouabaine (isoformes 3) apres 6h d'ischemie. A distance du foyer, des modifications de densite de liaison sont observees dans les regions sous-corticales (thalamiques et striatales) directement connectees a la zone lesee. L'existence d'alterations selectives des differentes isoformes de la na#+, k#+-atpase pourrait refleter la mise en place d'un mecanisme adaptatif a l'ischemie. Ce mecanisme adaptatif permettrait de limiter l'alteration des gradients ioniques induite apres ischemie. La liaison de ligands specifiques des differentes isoformes pourrait constituer en clinique, un index selectif a la fois de la mort neuronale induite apres ischemie dans la zone infarcie et des alterations fonctionnelles des structures sous-corticales.
47
Joseph, Christy [Verfasser]. "Neuroprotection by prolonged hypothermia induced by hydrogen sulphide in focal cerebral ischemic rat model: Evidence from electrocortical activity and recruitment of polymorphonuclear cells / Christy Joseph". Greifswald : Universitätsbibliothek Greifswald, 2012. http://d-nb.info/1027393888/34.
48
Guegan, Christelle. "Etude de l'apoptose et du role neuroprotecteur du nerve growth factor (ngf) lors d'une ischemie cerebrale focale permanente chez la souris". Caen, 1999. http://www.theses.fr/1999CAEN2022.
Resumen
Lors de pathologies, les cellules nerveuses peuvent mourir par apoptose, forme de mort programmee necessitant des processus cellulaires actifs. Les mecanismes moleculaires de la mort neuronale apres ischemie cerebrale sont encore mal connus ; nous les avons etudies dans un modele d'ischemie focale permanente realisee par electrocoagulation de l'artere cerebrale moyenne chez la souris. La perte neuronale touche exclusivement le cortex temporo-parietal gauche. Notre etude montre que des neurones dans la zone infarcie presentent des caracteristiques morphologiques et biochimiques de l'apoptose. Cette mort est une composante importante de la perte neuronale puisqu'elle participe a l'expansion de l'infarctus. L'etude de l'expression d'une proteine de regulation du cycle cellulaire, la cycline d1, ainsi que du facteur de transcription c-jun, montre que ces proteines peuvent constituer des mediateurs de la mort neuronale. Dans ce modele, plusieurs voies neuroprotectrices non exclusives sont recrutees : anti-apoptotique (expression de bcl-2), anti-oxydante (activite enzymatique de la glutathion peroxydase), et neurotrophique (augmentation du contenu en nerve growth factor (ngf). L'expression des recepteurs de basse (p75 n t r) et de haute (trka) affinite pour le ngf est induite dans les neurones corticaux apres ischemie. P75 n t r serait plutot associe a un signal de mort apoptotique, contrairement au recepteur de haute affinite. L'utilisation d'une lignee de souris transgeniques (tg) dans lesquelles le transgene codant pour le ngf est inductible notamment par un choc ischemique montre que ces souris presentent une reduction de 40% du volume de l'infarctus par rapport a des souris sauvages (wt), ainsi qu'une diminution de 30% de la densite de profils apoptotiques. De plus, ces souris possedent une resistance intrinseque aux chocs oxydatifs, et un pool energetique plus eleve que les souris wt. La modulation de l'apoptose observee chez les souris tg apres ischemie pourrait etre en relation avec l'augmentation de l'activite de la mn sod, enzyme anti-oxydante possedant aussi une action anti-apoptotique. Ces resultats soulignent la complexite des mecanismes neuroprotecteurs mis en jeu apres ischemie cerebrale.
49
Margaill, Isabelle. "Etude du rôle du glutamate et du monoxyde d'azote dans l'ischémie cérébrale focale transitoire chez le rat". Paris 5, 1996. http://www.theses.fr/1996PA05P616.
50
Gaignard, Pauline. "Métabolisme mitochondrial cérébral chez les mâles et les femelles : rôle des stéroïdes endogènes et effet de la progestérone après ischémie transitoire focale". Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T029.
Resumen
Les stéroïdes sexuels ne sont pas impliqués uniquement dans la reproduction, ils sont également actifs dans le système nerveux où ils exercent des effets neuroprotecteurs. La mitochondrie a un rôle central dans la synthèse de l’énergie cellulaire et le contrôle du stress oxydant. Ces fonctions mitochondriales seraient une cible potentielle des effets des stéroïdes sexuels dans le cerveau. Deux approches ont été développées au cours de ce travail de thèse : une approche physiologique avec l’étude de l’influence des stéroïdes endogènes sur la fonction mitochondriale cérébrale et une approche thérapeutique en utilisant le modèle expérimental de l’ischémie cérébrale et du traitement par la progestérone. Pour analyser l’influence des stéroïdes endogènes, nous avons comparé le fonctionnement de la phosphorylation oxydative (consommation d’oxygène ou « respiration » et activités enzymatiques) ; le niveau du stress oxydant (pool de glutathion mitochondrial et inactivation oxydative de l’aconitase mitochondriale) et les taux cérébraux de stéroïdes dans des groupes de souris mâles et femelles soit jeunes adultes intactes ou gonadectomisées (3 mois) ; soit âgées (20 mois). Nous avons montré que la respiration NADH-dépendante est plus importante et que le stress oxydant mitochondrial est moins important chez les femelles que chez les mâles jeunes. Cette différence n’existe plus chez les souris âgées et est abolie après ovariectomie mais pas après orchidectomie, ce qui démontre l’influence des stéroïdes ovariens. Les taux cérébraux importants de prégnènolone et de progestérone chez les souris jeunes femelles par rapport aux jeunes mâles pourraient être impliqués dans le dimorphisme sexuel observé.Les modifications de la respiration mitochondriale induites par l’ischémie cérébrale sont également différentes entre les mâles et les femelles dans notre modèle. La respiration NADH-dépendante est diminuée dans les deux sexes, mais la respiration FADH2-dépendante est diminuée spécifiquement chez les femelles. Le stress oxydant mitochondrial est augmenté dans les deux sexes. L’administration de progestérone permet de restaurer la respiration FADH2-dépendante chez les femelles et la respiration NADH-dépendante ainsi que le pool de glutathion mitochondrial dans les deux sexes. Ce travail a permis de mettre en évidence des différences de fonctionnement mitochondrial cérébral chez les souris mâles et femelles jeunes et d’identifier la phosphorylation oxydative et le stress oxydant mitochondrial comme cibles d’action des effets neuroprotecteurs de la progestérone lors de l’ischémie cérébraleBesides the reproduction control, sex steroids also act on nervous system and exert neuroprotective effects. The mitochondria are centrally involved in cellular energy synthesis and oxidative stress regulation and constitute a potential target of steroids effects on brain. The aim of our study was twofold: (1) to study the influence of endogenous steroids on brain mitochondrial function in physiological conditions ; (2) to determine the effects of progesterone on mitochondrial function when used as therapeutic agent in an experimental model of cerebral ischemia. To analyze the influence of endogenous sex steroids, the oxidative phosphorylation system (oxygen consumption or “respiration” and enzymatic activities) and mitochondrial oxidative stress (glutathione pool and mitochondrial aconitase oxidative inactivation) were analyzed in brain mitochondria of young adult male and female mice (3-month-old), intact and after gonadectomy, and of aged male and female mice (20-month-old). Our results showed that young adult females have lower oxidative stress and a higher NADH-linked respiration rate as compared to young adult males. This sex difference was suppressed by ovariectomy but not by orchidectomy and no longer existed in aged mice. Concomitant analysis of brain steroids suggest that the major male/female differences in brain pregnenolone and progesterone levels may contribute to the sex differences observed in brain mitochondrial function.We have also shown that the decrease of brain mitochondrial respiration induced by ischemia is different according to sex in our experimental model. The NADH-linked respiration decreased after ischemia in males and female but a decrease of FADH2-linked respiration only occurred in females. Ischemia induced oxidative damages in both males and females. Progesterone restored NADH-linked respiration in both sexes and FADH2-linked respiration in females. Progesterone also preserved mitochondrial glutathione pool in both sexes. Our findings point to a sex difference in brain mitochondrial function of young male and female mice and identify the oxidative phosphorylation system and the mitochondrial oxidative stress as targets of the neuroprotective effects of progesterone