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Du, Ying. "Ischemic and pharmacological preconditioning of rat myocardium : effects on ischemia-reperfusion injury /." View abstract or full-text, 2005. http://library.ust.hk/cgi/db/thesis.pl?BICH%202005%20DU.
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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.
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Dowden, Jennifer. "Characterizing the neuroprotective efficacy of ischemic preconditioning (ischemic tolerance) : is age an important factor? /." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0019/NQ54834.pdf.
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Harhous, Zeina. "Deciphering the Interlink between STAT3 and MAPKs in Ischemia/Reperfusion and Ischemic Conditioning." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1145.
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Les maladies cardiovasculaires sont une des principales causes de morbidité et de mortalité au monde. La plus courante est l’infarctus du myocarde définit pathologiquement par la mortalité cellulaire dû à une ischémie prolongée d’une partie du ventricule gauche. L'ischémie est caractérisée par un apport sanguin insuffisant causé par une obstruction d’une artère coronaire. La restauration, en clinique, du flux sanguin, appelée reperfusion, est considérée comme la méthode la plus efficace contre les dommages ischémiques. Paradoxalement, cette restauration du flux sanguin est associée à une exacerbation de la lésion tissulaire, entraînant alors des lésions d'ischémie-reperfusion (I/R). Dans le but de limiter ces lésions, le conditionnement ischémique myocardique est une avancée majeure dans le domaine de la cardioprotection. Ce protocole confère ses effets cardioprotecteurs via le recrutement de divers mécanismes endogènes suivant l’activation de deux voies intracellulaires : la voie RISK (Reperfusion Injury Salvage Kinase) et/ou la voie SAFE (Survivor Activator Factor Enhancer). Ces voies impliquent l'activation de différentes cascades de signalisation et de protéines kinases. En particulier, concernant la voie SAFE, le transducteur de signal et l'activateur de transcription-3 STAT3, a été identifié comme un acteur clé dans le postconditionnement ischémique (PostCI). Il est suggéré que les effets cardioprotecteurs attribués à STAT3 soient liés à ses effets en tant que facteur de transcription et en tant que régulateur de l’activité mitochondriale, mais tout n’est pas encore connu. En revanche, il est admis que STAT3 est activé par la phosphorylation ciblant les résidus tyrosine 705 et sérine 727. Dans nos travaux actuels, nous avions initialement pour objectif d’étudier les rôles cardioprotecteurs mitochondriaux de STAT3 après une I/R et un PostCI. Cependant, nous n'avons pas été en mesure de détecter STAT3 dans les mitochondries de cardiomyocytes adultes de souris, dans des conditions basales et de stress, en utilisant différentes approches. Fait intéressant, nous avons montré une localisation exclusive de STAT3 dans les myocytes cardiaques adultes, le long des tubules T, et nous avons mis en évidence les inconvénients des techniques précédemment utilisées.Outre les rôles putatifs de STAT3 dans les mitochondries, nous avons ciblé ses effets dans la signalisation et la génomique au cours de l'I/R et du PostCI. Nous avons tout d’abord cherché à déterminer, pendant l’I/R et le PostCI, la cinétique temporelle d’activation de STAT3 et des autres kinases de la voie RISK, notamment Akt et les MAPK ERK1 / 2, JNK et p38. En outre, nous avions pour objectif d’étudier les liens entre les voies SAFE et RISK en déchiffrant les liens entre STAT3 et les kinases RISK au cours du PostCI. Nous avons montré qu’après une ischémie et un temps court de reperfusion, STAT3 et ERK1/2 sont activés, et que l’utilisation d’un PostCI active d’autant plus STAT3 en induisant exclusivement la phosphorylation de sa tyrosine. Nous avons également montré que l’interconnexion entre les voies SAFE et RISK, dans le protocole PostCI utilisé, se fait par STAT3 et ERK1/2. À partir de ces résultats, nous nous sommes dirigés vers la génomique grâce à laquelle nous avons étudié l'activité de STAT3 au cours de l'IPoC. À cet égard, nous avons montré que STAT3 est impliqué dans la régulation de la réponse inflammatoire au cours de la PostCI. Dans l’ensemble, cette étude présente une approche globale des fonctions mitochondriales, de signalisation et génomiques de STAT3 dans le contexte de la protection cardiaque<br>Cardiovascular diseases are leading causes of morbidity and mortality worldwide. Among the mostly prevailing cardiovascular diseases is myocardial infarction, which is pathologically defined as myocardial death due to a prolonged ischemia. Ischemia is an insufficient supply of blood caused by a blockade in the coronary arteries. The early restoration of blood flow is considered the most effective method against the ischemic lesions. Paradoxically, this blood flow restoration is associated with an exacerbation of the tissue injury, leading to the ischemia-reperfusion (I/R) injury. To avoid this injury, the myocardial ischemic conditioning protocol has rejuvenated the field of cardioprotection. This protocol confers its cardioprotective effects via recruiting various endogenous mechanisms following the activation of two intracellular pathways: the reperfusion injury salvage kinase (RISK) or survivor activator factor enhancer (SAFE) pathways. These pathways involve the activation of different signaling cascades and protein kinases. Zooming in through the SAFE pathway, the signal transducer and activator of transcription-3, STAT3, has been identified as a prominent key player in ischemic postconditioning (IPoC). The cardioprotective effects attributed to STAT3 are suggested to be linked to its roles as a transcription factor and as a regulator of the mitochondrial activity, but these are not well studied and elaborated. STAT3 is activated by phosphorylation, which targets the tyrosine 705 and serine 727 residues. In our current work, we initially aimed to investigate the mitochondrial cardioprotective roles of STAT3 following I/R and IPoC. However, we were not able to detect STAT3 in the mitochondria of adult mouse cardiomyocytes under variousbasal and stress conditions using different approaches. Interestingly, we showed an exclusive STAT3 pattern in adult cardiac myocytes, along the T-tubules, and highlighted drawbacks of previously used techniques. Aside from the mitochondrial roles of STAT3, we targeted its signaling and genomic roles during I/R and IPoC. We first aimed to determine, during I/R and IPoC, the temporal kinetics of activation of STAT3 and the other kinases of the RISK pathway including Akt and the MAPKs ERK1/2, JNK and p38. In addition, we aimed to decipher the interlink between the SAFE and RISK pathways through deciphering the interlink between STAT3 and the RISK kinases following IPoC. We showed that a short reperfusion time activates STAT3 and ERK1/2 following ischemia, and that the application of IPoC further activates STAT3 through inducing its tyrosine phosphorylation. We also showed that the interlink between SAFE and RISK pathways, in the IPoC protocol we used, is through STAT3 and ERK1/2. From this signaling level, we moved toward the genomic level whereby we investigated the genomic activity of STAT3 during IPoC. In this regard, we have shown that STAT3 is involved in the regulation of the inflammatory response during IPoC. Overall, this study presents a global approach of STAT3’s mitochondrial, signaling and genomic functions in the context of cardiac protection
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Zhang, Jitian. "Nebulized phosphodiesterase 3 inhibitor during warm ischemia attenuates pulmonary ischemia-reperfusion injury." Kyoto University, 2009. http://hdl.handle.net/2433/126442.
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Li, Yan. "Inhibitory synpatic transmission in striatal neurons after transient cerebral ischemia." Connect to resource online, 2009. http://hdl.handle.net/1805/2021.
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Thesis (Ph.D.)--Indiana University, 2009.<br>Title from screen (viewed on December 1, 2009). Department of Anatomy and Cell Biology, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Zao C. Xu, Feng C. Zhou, Charles R. Yang, Theodore R. Cummins. Includes vitae. Includes bibliographical references (leaves 115-135).
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Keasey, Matthew P. "MicroRNAs in Cerebral Ischemia." Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526014.
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Lipšic, Erik. "Erythropoietin in cardiac ischemia." [S.l. : [Groningen : s.n.] ; University Library Groningen] [Host], 2006. http://irs.ub.rug.nl/ppn/293076030.
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Aoyama, Akihiro. "Post-ischemic Infusion of Atrial Natriuretic Peptide Attenuates Warm Ischemia-Reperfusion Injury in Rat Lung." Kyoto University, 2011. http://hdl.handle.net/2433/142544.
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Hultgren, Rebecka. "Lower limb ischemia in women /." Stockholm, 2004. http://diss.kib.ki.se/2003/91-7349-798-3.
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Molnar, Maria. "Hyperglycemia in Experimental Cerebral Ischemia." Doctoral thesis, Uppsala universitet, Anestesiologi och intensivvård, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-247763.
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Cerebral ischemia is a life-threatening condition associated with a substantial morbidity and mortality. Hyperglycemia, a common coexisting phenomenon in both stroke and cardiac arrest (CA), may further aggravate ischemic brain injury. To date, the therapeutic possibilities are lim-ited and the search for new treatment modalities is warranted. One aspect of such a research could be to better understand the cerebral pathogenesis induced by hyperglycemic ischemia-reperfusion. We investigated the combination of ischemia and hyperglycemia in two experimental models of stroke and CA. The aims were to test the neuroprotective potential of the sulfonated nitrone 2-sulfophenyl-N-tert-butylnitrone (S-PBN) in focal hyperglycemic cerebral ischemia (1), to outline the short-terms effects of hyperglycemia in prolonged (2) and short CA (3) and to performed a global transcriptome analysis of brain from hyperglycemic and normoglycemic CA (4). In a stroke model rats were made hyperglycemic prior to transient middle cerebral artery oc-clusion and randomized to S-PBN or saline. We found that S-PBN may ameliorate hyperglyce-mic-ischemic brain damage by improving the neurological performance after 1 day of survival, but did not reduce the infarct size. To study the cerebral oxidative state and perfusion after CA, pigs were randomized and clamped at blood glucose levels of 8.5 ̶ 10.0 mmol/L (high) and 4.0 ̶ 5.5 mmol/L (normal), sub-jected to 12 ̶ min of CA, followed by 8 min of cardiopulmonary resuscitation (CPR), and ob-served for 180 min. Increased oxygenation was found at higher glucose levels measured by near-infrared light spec-troscopy after CA. Tendencies toward increased protein S100β and 15-keto-dihydro-prostaglandin F2α were observed in the hyperglycemic group. We hypothesized that in combination with a brief period of CA, the preischemic hyperglycemia would worsen the cerebral injury compared with normoglycemia. We used a glycemic protocol similar to that in Paper II, whereby pigs were subjected to 5 ̶ min of CA, followed by 8 min of CPR, and observed for 180 mins. An increased level of the cerebral marker S100β was found in hyperglycemic pigs compared with normoglycemic pigs after CA. Global transcriptome analysis using microarray analysis revealed a different early metabolic gene expression in hyperglycemic CA compared with normoglycemic CA.
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Alrabadi, Nasr Nofal Salieba. "Novel Pharmacological Approaches for Understanding and Modulating the Pathology of Ischemic Heart Disease." Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/15926.
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Over the last century, ischemic heart diseases (IHD) have been the worldwide leading cause of death. Major improvement in the prevalence and prognosis of IHD is dominantly related to the modulation of disease (atherosclerosis) risk factors rather than developing pharmacological approaches to treatment. Excessive inflammatory response, especially after ischemia-reperfusion injury (IR), represents a key feature in the progressive pathology of IHD. The kinetics of this inflammatory infiltration is well organized in a timely manner. Both the classical pathological phases of post ischemic heart injury and the process of healing are defined based on this cascade of inflammatory responses. However, the pathological demarcation between the harmful and healing responses is not well understood. Successful treatments in blocking excessive inflammatory responses and providing functional advantages in animal models, all failed in proving applicable clinical benefits. This disappointing outcome over the last 30 years has dampened the current vision related to the inflammatory response, thus, further understanding into this pathological process is needed. The basic scientific motivation for designing targeted-nanocarriers is to provide a tolerable and non-toxic nanocarrier system which can encapsulate cardio protective agents and transport them specifically to the ischemic tissue; thus overcoming all of the biological barriers. Moreover these targeted-nanocarriers aim to deliver the therapy to the specific site of the pathological process in a timely fashion, avoiding any pharmacokinetic problems, achieve effective therapeutic concentrations and reduce any cytotoxicity or unwanted side effects. Alternatively, they can act to target the pathological condition by selectively blocking the recruitment of harmful cells to the pathological site. To test targeted delivery, in this thesis, we present data on the biocompatible/biodegradable fungal protein (so called; RodA-hydrophobin) which was modified by incorporating the ischemic myocardium targeted peptide sequence “STSMLKA”. To test selective blocking of the pathological response, we studied Immunomodulatory microparticles (IMPs) and tested whether they indeed have the ability to modulate the ischemic injury by trafficking the inflammatory monocytes away from the site of injury (ischemic heart) as had been proposed by recent work from our institute. xiii The results of this thesis show for the first time that we were able to develop a flow cytometry kinetic model incorporating the blood, spleen and heart in a rat model of IR. When guided by our histological and IHC work, we found that the flow cytometry-leucocyte percentages and relative ratios within the circulation can be more predictive than their absolute counts as to the pathological changes occurring in the heart after the IR injury. Our study suggests that the leucocyte absolute counts can over-estimate the pathological role of the inflammatory response after the IR injury, thus misleading the beneficial effect of proposed treatments. Thus, our findings may have the potential to explain the failure in the clinical translation of the Immunomodulatory therapeutics within the field of IHD. The IMP treatment did not show any beneficial effect, did not reduce the inflammatory response, and unexpectedly, seemed to result in aggregation/clumping at site of vasculature. Thus, further study is required to understand the mode of action (MOA) of IMPs before clinical applications. The feasibility of designing RodA-based nanocarriers (polymers) with or without protein modifications is shown and that they have a biocompatible nature was derived by studying cultured heart cells (H9c2 cells). Unfortunately, our modified- RodA protein (after incorporating the targeted peptide sequence within the RodA structure) did not confer any preferential increase of RodA binding to the ischemic H9c2 cells or to the ischemic heart tissue from our rat model of 3 or 5 days AMI and IR injuries. However, the wild type RodA hydrophobin was able to target the ischemic heart tissue. Our study suggested that this targeting ability may be related to the progressive death of cardiomyocytes and possibly related to the α-helix region within the RodAhydrophobin structure.
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MACRI', MARIA LOREDANA. "Ruolo dello scambiatore Na+/Ca2+ nel precondizionamento ischemico in modelli sperimentali di ischemia-riperfusione cardiaca." Doctoral thesis, Università Politecnica delle Marche, 2015. http://hdl.handle.net/11566/242929.
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L’ischemia cardiaca è una delle principali cause di morbidità e mortalità nei Paesi occidentali. Alterazioni dei sistemi di trasporto del calcio cardiaco che causano aumento di calcio citosolico sono i principali responsabili del danno da I/R. Il precondizionamento ischemico (IPC) conferisce cardioprotezione attenuando tale aumento. Uno dei principali responsabili del controllo dell’omeostasi del calcio cellulare nel cuore è NCX1. Durante l’I/R, NCX1 induce l’influsso di Ca2+, pertanto per poterlo contrastare si potrebbe utilizzare l’inibitore SN6.
Lo scopo del presente studio è stato di studiare il ruolo potenziale che NCX1 gioca nel PC nei cardiomiociti,nel cuore isolato di ratto e nelle H9c2-wt ed H9c2 NCX1.
In tutti questi modelli I/R era in grado di indurre citotossicità cellulare mentre l’SN6 la preveniva. Il PC preveniva la tossicità cellulare mentre l’SN6 era in grado di abolire tale effetto cardioprotettivo. Dall’analisi dell’espressione proteica è risultato che NCX1 aumenta sia nell’IPc che nell’I/R. Tale aumento veniva completamente revertito dall’SN6. In conclusione la presente tesi suggerisce che NCX1 gioca un ruolo inportante nel IPC e che il blocco della sua attività potrebbe esercitare effetti protettivi.<br>Ischemic heart diseases are a major cause of morbidity and mortality in western nations. Defects in myocardial Ca2+ transport system with cytosolic Ca2+ overload is a major contributor to myocardial ischemia/reperfusion (I/R) injury. Ischemic preconditioning (IPC) is well known to confer cardioprotection against myocardial I/R injury attenuating the cytosolic Ca2+ overload. One of the key players for the maintenance of [Ca2+]i homeostasis in the heart is the sodium/calcium exchanger 1 (NCX1). During IR, NCX induces Ca2+ influx, which strengthens Ca2+ overload. SN-6, a benzyloxyphenyl derivative and proposed selective NCX1 inhibitor, could be used to prevent I/R injury.
The present study aimed at evaluating the potential role of NCX1 during ischemic preconditioning in isolated rat ventricular myocyctes, hearts and in a cellular cell line model (H9c2 wilde-type and a stable transfected with NCX1.
In all the models the I/R was observed an increased cell toxicity and the SN6 was able to revert this effect. Subseqyently, isolated rat ventricular myocytes and whole hearts were subjected to PI/R. the results obtained suggests that the exposure to PC before I/R improved cell viability and reduced is-chemic areas. The inhibition of the reverse mode of the NCX1 by SN-6 during PC abolished the cardioprotection observed in I/R alone.
Furthemore, in isolated rat ventricular myocytes and whole hearts, was observed that PC and I/R alone were able to induce an increased protein levels of NCX1. This effect was completely reverted by SN6. The exposure to PC before I/R induced NCX1 protein levels greater than PC and I/R alone. The presences of SN6, in whole hearts, reverted this effect. In conclusion, the present thesis sug-gests that NCX1 may play an important role in PC reducing the cell toxicity induced by I/R.
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Tupling, Allan Russell. "Effects of ischemia and ischemia-reperfusion on sarcoplasmic reticulum structure and function in rat skeletal muscle." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ53520.pdf.
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Yamasaki, Kenzou. "Preconditioning with 15-min ischemia extends myocardial infarct size after subsequent 30-min ischemia in rabbits." Kyoto University, 1997. http://hdl.handle.net/2433/202231.
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Fröjse, Rolf. "Exploring Intestinal Ischemia : An experimental study." Doctoral thesis, Umeå universitet, Kirurgisk och perioperativ vetenskap, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-461.
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Background and aims: Unrecognized intestinal mucosal ischemia in severely ill patients may trigger development of multiple organ failure. Such ischemia can be evaluated by intraluminal tonometry reflecting mucosal PCO2 and intramucosal pH (pHi). The aims were to develop an apparatus for continuous saline tonometry (CST), to analyse circulatory control mechanisms during intestinal hypoperfusion and to evaluate the effect of dopexamine on intestinal circulation. Methods: A modified standard tonometry catheter was integrated in a closed system with circulating saline. By measuring saline PCO2 in a measurement unit pHi could be calculated. This novel system was tested in vitro and in vivo. In a porcine study, CST was evaluated against standard saline tonometry, tissue oxygenation (PO2 TISSUE), jejunal mucosal perfusion (laser doppler flowmetry; LDF) and mesenteric net lactate flux during graded reductions of superior mesenteric arterial pressure (PSMA). Local control mechanisms for maintenance of intestinal oxygenation were analysed. Effects of dopexamine on the intestinal vascular bed were explored. Mucosal lactate production was assessed by microdialysis. Results: CST measured accurate PCO2 values and changes in pHi during restricted intestinal circulation and at reperfusion. Local control mechanisms were insufficient at a PSMA of 30 mmHg, pHi was reduced to 7.10 and intestinal net lactate production was demonstrated. Absence of anaerobic intestinal metabolism was verified at PSMA ≥ 50 mmHg, pHi ≥ 7.22 and a PCO2 gap ≤ 15.8 mmHg. Dopexamine induced negative regional metabolic effects at the lowest PSMA, as expressed by decreased PO2 TISSUE and pHi, increased PCO2 gap and intestinal net lactate production. Conclusions: CST reflected changes in pHi, induced by intestinal hypoperfusion and at reperfusion. Levels of PSMA, pHi and PCO2 gap as indicators of aerobic conditions were defined. Dopexamine induced a decrease of PO2 TISSUE and pHi as well as an increase in lactate flux at the lowest PSMA level.
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Abunasra, Haitham Juma. "Gene therapy in myocardial ischemia-reperfusion." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404964.
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Bonneville, Marika. "Endocannabinoid Modulation of Post-Ischemia Depression." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35056.
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Post-ischemia depression (PID) is a condition that affects approximately 30% of survivors from stroke or cardiac arrest and has an important impact on patients’ quality of life. Previous studies support important roles of the endocannabinoid (eCB) system in depression and brain ischemia. This study attempts to link all three variables together by investigating the role and mechanism of eCB signaling in the development of PID. A global ischemia + hypotension model was used to induce a PID phenotype in CD1 mice. Three ischemic time frames were tested, and even though all three could induce significant cell death in the CA1 region of the hippocampus, only the 15-minute time point led to an increased immobility time on the forced swimming test (FST). The main goal of this study was to investigate the effect of a cannabinoid type-I receptor (CB1R) antagonist/inverse agonist, AM281, on the development of two depressive symptoms: anhedonia, measured with the sucrose preference test (SPT), and behavioral despair, measured with the FST. AM281 administration was able to significantly reduce the symptoms of anhedonia and behavioural despair. Subsequently, the mechanism behind this antidepressant-like effect was investigated. Administration of bicuculine with AM281 did not significantly affect the antidepressant effect on the FST, therefore suggesting that AM281 does not act on GABAergic synapses. A similar protocol was adopted with NVP-AM077, where its administration combined with AM281 was able to block the effect of AM281, thus confirming the importance of glutamatergic synapses for the antidepressant effect of AM281. Furthermore, the administration of a TAT-GLUR2 peptide did not significantly affect the effect of AM281, implying that the astroglial cell-mediated LTD (long-term depression) at glutamatergic synapses is not involved in the antidepressant effects of AM281. Finally, a bilateral intra-BLA (basolateral nucleus of the amygdala) administration of AM281 was able to reduce the immobility time on the FST. In conclusion, these results highlight the important contribution of BLA glutamatergic synapses to the antidepressant-like effect conferred by AM281.
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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.
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Soundarapandian, Mangala Meenakshi. "Glutamate Excitotoxicity in Epilepsy and Ischemia." Doctoral diss., University of Central Florida, 2007. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/3169.
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'Excitotoxicity' represents the excitatory amino acid mediated degeneration of neurons. Glutamate is the major excitatory neurotransmitter in the brain. Glutamate excitotoxicity has been implicated in a number of neurodegenerative disorders like Stroke, Epilepsy, Alzheimer's disease and traumatic brain injury. This neurotoxicity is summed up by the 'glutamate hypothesis' which describes the cause of neuronal cell death as an excessive release of glutamate causing over excitation of the glutamate receptors and subsequent increase in influx of calcium leading to cell death. An effort to counteract this neurotoxicity has lead to the development of glutamate receptor antagonists that can effectively serve as neuroprotective agents. Nevertheless, the downside to these drugs has been the side effects observed in clinical trial patients due to their disruptive action on the physiological function of these receptors like learning and memory. This work was undertaken to identify targets that can effectively be used to treat excitotoxicity without affecting any normal physiological functions. In one approach, (chapter I) we have identified the KATP channels as an effective modulator of epileptogenesis. In another approach, (Chapter II) we show that targeting the AMPA receptor subunit GluR2 is a practical strategy for stroke therapy. KATP channels that are gated by intracellular ATP/ADP concentrations are a unique subtype of potassium channels and play an essential role in coupling intracellular metabolic events to electrical activity. Opening of KATP channels during energy deficits in the central nervous system (CNS) induces efflux of potassium ions and in turn hyperpolarizes neurons. Thus, activation of KATP channels is thought to be able to counteract excitatory insults and protect against neuronal death. Here, we show that, functional Kir6.1 channels are located at excitatory pre-synaptic terminals as a complex with type-1 Sulfonylurea receptors (SUR1) in the hippocampus. The mutant mice with deficiencies in expressing the Kir6.1 or the SUR1 gene are more vulnerable to generation of epileptic form of seizures, compared to wild-type controls. Whole-cell patch clamp recordings demonstrate that genetic deletion of the Kir6.1/SUR1 channels enhances glutamate release at CA3 synapses. Hence, expression of functional Kir6.1/SUR1 channels inhibits seizure responses and possibly acts via limiting excitatory glutamate release. In addition to epilepsy, ischemic stroke is a leading cause of death in developed countries. A critical feature of this disease is a highly selective pattern of neuronal loss; certain identifiable subsets of neurons, particularly CA1 pyramidal neurons in the hippocampus are severely damaged, whereas others remain intact. A key step in this selective neuronal injury is Ca2+/Zn2+ entry into vulnerable neurons through [alpha]-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels, a principle subtype of glutamate receptors. AMPA receptor channels are assembled from glutamate receptor (GluR) -1, -2, -3, and -4 subunits. Circumstance data have indicated that the GluR2 subunits dictate Ca2+/Zn2+ permeability of AMPA receptor channels and gate injurious Ca2+/Zn2+ signals in vulnerable neurons. Here we show that ischemic insults induce toxic Ca2+ entry through AMPA receptors into vulnerable neurons by modification of GluR2 RNA editing. Thus, targeting of GluR2 subunit can be considered as a promising target for stroke therapy.<br>Ph.D.<br>Department of Biomolecular Science<br>Burnett College of Biomedical Sciences<br>Biomolecular Sciences PhD
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Aluri, Hema. "INTRA-MITOCHONDRIAL INJURY DURING ISCHEMIA-REPERFUSION." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/474.
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Cardiac injury is increased following ischemia-reperfusion. Mitochondria are the “effector organelles” that are damaged during ischemia (ISC) when there is no blood flow. Resumption of metabolism by damaged mitochondria during reperfusion (REP) results in increased cell injury. Current therapeutic interventions to pre-condition and post-condition the heart during ISC are ineffective during certain conditions like aging and diabetes due to defects in the signaling cascades. In contrast, mitochondrial-based strategies are effective in protecting the heart during ISC-REP. Hence direct therapeutic targeting of dysfunctional mitochondria will provide the potential to bypass the upstream signaling defects and intervene directly upon the effector organelle. Novel mitochondrial-targeted therapy relies on understanding the sites in the electron transport chain (ETC) that are damaged by ISC and produce cell-injury during REP. This project identifies a novel pathological role of cytochrome c in depleting cardiolipin during ischemia after which the mitochondria are in a defective condition that leads to additional cell death during reperfusion. During ischemia oxidants from complex III oxidize cytochrome c, forming a peroxidase, which causes oxidative damage and depletion of cardiolipin. Depletion of cardiolipin disrupts normal physiology and augments cell death. Identification of the innovative pathobiology during ISC-REP recognizes a novel therapeutic target, cytochrome c peroxidase, which can be a focal point for new therapeutic interventions to decrease cardiac injury. In order to maintain homeostatis, living organisms have the methionine sulfoxide reductase system, which reduce both free and protein bound Met(O) back to methionine (Met) in the presence of thioredoxin. Oxidized Trx is inactive and unable to bind to ASK1 thereby activating ASK1 and causing cell death via p38/JNK pathways thereby contributing to the pathogenesis of myocardial ISC-REP injury. In this study we have shown that inhibition of ASK1 protects the heart during REP via the modulation of mitochondria that sustained damage during ISC. The mitochondrial-based mechanism of cardioprotection with ASK1 inhibition enhanced the functional integrity of the inner mitochondrial membrane retaining cytochrome c thereby decreasing cell death. This therapeutic intervention is a key step to achieve the ultimate goal to improve clinical outcomes in patients that suffer an acute myocardial infarction.
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Todd, Michael. "The effects of multiple ischemia and survival times on hippocampal CA1 neuronal cell loss in a rat model of global ischemia: A long-term ischemia maturation study." Thesis, University of Ottawa (Canada), 1998. http://hdl.handle.net/10393/4230.
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We investigated the effects of varying ischemia and survival times on CA1 neuronal loss. Histological analysis of the hippocampus was performed at 2, 7, 14, 28 and 90 days following 3, 5, 7, 10 and 13 minutes of global forebrain ischemia. Our results indicate that the ischemic maturation process extends beyond 7 days. Ten and thirteen minutes of ischemia produced a significant degree of cell loss by 7 days (70.53% and 83.25% respectively), while average cell death at 90 days survival was approximately 12% higher. Most strikingly, seven minutes of ischemia produced approximately 30% CA1 cell loss at 90 days compared to only 3% cell loss at 7 days, a nine-fold increase. No cell loss was observed at 2 and 7 days survival following 5 minutes of ischemia, but an average of 5.6% cell loss was observed at 3 months. Three minutes of ischemia produced no cell damage. Data collapsed over ischemic severity suggested that there may 2 rates of cell death evident in this study: (1) a rapid cell loss occurring within the first 7 days of ischemia and (2) a slow progressive cell loss occurring over weeks. Ten and thirteen minutes of ischemia possessed the rapid cell death, while 7 minutes appeared to display only slow progressive cell loss. The fact that the ischemic maturation process extends well beyond 7 days and that mild ischemia severities can produce significant cell loss at long survival times holds important implications for drug trials and our current knowledge of death mechanisms. (Abstract shortened by UMI.)
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Todd, Mike. "The effects of multiple ischemia and survival times on hippocampal CA1 neuronal cell loss in a rat model of global ischemia, a long-term ischemia maturation study." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ36746.pdf.
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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.
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Adhami, Faisal. "Differential Adult and Neonatal Response to Cerebral Ischemia-Hypoxia." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1196054266.
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Zouita, Abdel Hakim. "Ischemia modified-albumin as a biomarker of myocardial ischemia : early diagnosis of acute coronary syndrome and cost effectiveness analysis." Thesis, University of Portsmouth, 2016. https://researchportal.port.ac.uk/portal/en/theses/ischemia-modifiedalbumin-as-a-biomarker-of-myocardial-ischemia(326d84fe-6bb8-463d-b7fc-00ad3dfbc6c8).html.
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Ischemia modified-albumin (IMA®) is a useful early cardiac biomarker for the diagnosis of acute coronary syndrome. In this study the diagnostic efficiency and the cost effectiveness of the oxidative stress biomarker (ischemia modified-albumin), myocardial necrosis (high sensitivity cardiac troponin, heart fatty-acid binding protein), vascular stress (copeptin) and myocardial dysfunction and hemodynamic stress (B-type natriuretic peptide) were evaluated for the diagnosis of acute myocardial infarction and cost benefit in low risk patients presenting to the emergency department with chest pain. This study was a retrospective observational study of a prospective randomised controlled trial. A surplus of well characterised blood samples were analysed for the above biomarkers. A meta-analysis study of the diagnostic performance of Ischemia modified-albumin assay in patients presenting with chest pain suggestive of acute coronary syndrome was conducted. The-cost-benefit analysis was based on doctor on demand scenario. Four hundred and forty-four samples were made available for this study, of which 174 patients had samples taken on admission and at 90 min. Three patients had a final diagnosis of acute myocardial infarction and one patient died. The difference in ischemia modified-albumin concentration was statistically significant (p = 0.002) between patients presenting on admission and at 90 min after admission. NT-pro-BNP had the highest diagnostic efficiency on admission with an area under the receiver operator curve (AUC) of 93% (95% CI, 82-93%). IMA did not reach the desired diagnostic efficiency with an AUC ranging from 54%-58%. The combined diagnostic efficiency of IMA plus high sensitivity cardiac troponin had a sensitivity and specificity of 71% (95% CI, 56-82%) and 100% (95% CI, 98-100%) respectively. The remaining biomarkers were not diagnostically efficient when combined with IMA. All biomarkers demonstrated poor prognostic value in predicating major adverse cardiac events within 30 days. Meta-analysis (n = 4295) demonstrated a sensitivity of 77.73% (95% CI, 72.21-83.24%) and specificity of 72.71% (95% CI, 64.09-81.34%) respectively. The negative predictive value and positive predictive was 80.13% (95% CI, 73.18-87.08%) and 67.91% (95% CI, 58.47-77.39%) respectively. The implementation of high sensitivity troponin plus IMA on admission would cost £638.00 per high-risk patient, compared to £464.00 for troponin alone as per current protocol. In conclusion, IMA plus high sensitivity cardiac troponin is cost effective and could be used to rule-out acute myocardial infarction. High sensitivity cardiac troponin is the most diagnostically efficient biomarker for early diagnosis of acute myocardial infarction. IMA assay alone is not suitable for the diagnosis of acute myocardial infarction.
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Venardos, Kylie M. "Myocardial Antioxidant Enzyme Systems, Ischemia-Reperfusion Injury, and Selenium." Thesis, Griffith University, 2005. http://hdl.handle.net/10072/365301.
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Coronary heart disease remains the greatest killer of Australian's, and given our ageing population, along with increasing risk factors, it is predicted to become an even more significant problem worldwide over the next 20 years. Reperfusion, without doubt is the most effective treatment for ischemic myocardium. However, this produces deleterious effects upon cells, and depending on the severity, may ultimately lead to cell death. While the pathogenesis of ischemia-reperfusion is not completely understood, there is considerable evidence implicating reactive oxygen species (ROS) as an initial cause of the injury. ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks, all potentially damaging to normal cellular function. ROS have been shown to be generated following routine clinical procedures such as coronary bypass surgery and thrombolysis, due to the unavoidable episode of ischemiareperfusion. Furthermore, they have been associated with poor cardiac recovery post-ischemia, with recent studies supporting a role for them in infarction, necrosis, apoptosis, arrhythmogenesis and endothelial dysfunction following ischemia-reperfusion. In normal physiological condition, ROS production is usually homeostatically controlled by endogenous free radical scavengers such as SOD, catalase, and the glutathione peroxidase
and thioredoxin reductase systems. Targeting the generation of ROS with various antioxidants has been shown to reduce injury following oxidative stress, and improve recovery from ischemia-reperfusion injury.
This thesis investigates the role of myocardial antioxidant enzymes in ischemiareperfusion injury, particularly the glutathione peroxidase (GPX) and the thioredoxin reductase (TxnRed) systems. GPX and TxnRed are selenocysteine dependent enzymes, and their activity is known to be dependent upon an adequate supply of dietary selenium and selenocysteine. In mammalian cells, the generation of selenocysteine occurs during amino acid biosynthesis and the degree of selenium (Se) incorporation into the cysteine residue is concentration dependent. Previous studies have found that up-regulation of these systems is cardioprotective and down-regulation is detrimental following ischemia-reperfusion. This thesis attempts to extend these observations by increasing not only our understanding of the roles of myocardial antioxidant enzymes in ischemia-reperfusion injury, but also the effect of dietary selenium on these systems. Furthermore, it investigates the effects of ischemia, reperfusion, and ageing on myocardial antioxidant enzymes.<br>Thesis (PhD Doctorate)<br>Doctor of Philosophy (PhD)<br>School of Health Sciences<br>Full Text
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McDonough, Jason L. "Myofilament protein modifications in myocardial ischemia/reperfusion." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2002. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ65682.pdf.
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Snoeckx, Luc Henricus Elisabeth Hyacinthus. "Ischemia tolerance of the hypertrophied rat heart." Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1987. http://arno.unimaas.nl/show.cgi?fid=5399.
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Nelissen-Vrancken, Henrica Johanna Maria Gerardine. "Local renin angiotensin systems and peripheral ischemia." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 1992. http://arno.unimaas.nl/show.cgi?fid=5719.
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Roekaerts, Paul M. H. J. "Alpha2-adrenergic receptor agonists in myocardial ischemia." [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 1997. http://arno.unimaas.nl/show.cgi?fid=5784.
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Lips, Jeroen. "Experimental spinal cord ischemia detection and protection /." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/62717.
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Winbladh, Anders. "Microdialysis in Liver Ischemia and Reperfusion injury." Doctoral thesis, Linköpings universitet, Kirurgi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-68651.
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Introduction: New chemotherapy regimens and improvements in surgical technique have increased the number of patients with liver tumours eligible for curative liver resection. There is a significant risk of bleeding during liver surgery, but this risk can be reduced if the portal inflow is temporarily closed; i.e. the Pringles maneuver (PM). If the PM is used, the liver will suffer from ischemia and reperfusion injury (IRI). If the liver remnant is too small or if the patient has chronic liver disease, the IRI may inhibit the regeneration of the liver remnant. The patient may then die from postoperative liver failure. Several strategies have been tried to protect the liver from IRI. For instance can the PM be applied in short intervals or reactive oxygen species can be scavenged by antioxidants. There are no sensitive methods available for studying IRI in patients and little is known how IRI affects the metabolism in the liver. Microdialysis is a technique that allows for continuous sampling of interstitial fluid in the organ of interest Aim: To investigate the effects of ischemia and reperfusion on glucose metabolism in the liver using the microdialysis technique. Method: A porcine model of segmental ischemia and reperfusion was developed. The hepatic perfusion and glucose metabolism was followed for 6-8 hours by placing microdialysis catheters in the liver parenchyma (studies I-III). In study IV, 16 patients were randomized to have 10 minutes of ischemic preconditioning prior to the liver resection, which was performed with 15 minutes of ischemia and 5 minutes of reperfusion repetitively until the tumour(s) were resected. Results: During ischemia the glucose metabolism was anaerobic in the ischemic segment, while the perfused segment had normal glucose metabolism. Urea was added in the perfusate of the microdialysis catheters and was found to be a reliable marker of liver perfusion. The antioxidant NAcetylcystein (NAC) improved the hepatic aerobic glucose metabolism in the pig during the reperfusion, shown as reduced levels of lactate and improved glycogenesis in the hepatocytes. This can be explained by the scavenging of nitric oxide by NAC as nitric oxide otherwise would inhibit mitochondrial respiration. Also IP improved aerobic glucose metabolism resulting in lower hepatic lactate levels in patients having major liver resections. Conclusion: Microdialysis can monitor the glucose metabolism both in animal experimental models and in patients during and after hepatectomy. Both NAC and IP improves aerobic glucose metabolism, which can be of value in patients with compromised liver function postoperatively.
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Björnsson, Bergþór. "Methods to Reduce Liver Ischemia/Reperfusion Injury." Doctoral thesis, Linköpings universitet, Institutionen för klinisk och experimentell medicin, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-110318.
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Introduction: During the last two decades, liver surgery has expanded enormously, partly due to improved surgical equipment and techniques as well as new and more powerful chemotherapy agents. As the liver is a very well-vascularized organ, there is an inherent risk of bleeding during liver resection. One of the most popular methods employed to reduce this risk is to close the vascular inflow to the liver using the Pringle’s maneuver (PM). However, this procedure has been recognized to cause ischemia/reperfusion injury (IRI) to the future liver remnant (FLR). In cases of extensive resection where the FLR is small and in cases when the liver suffers from chronic diseases, such as cirrhosis, IRI can greatly increase the risk of post-operative liver failure (POLF). Ischemic preconditioning (IPC) and, more recently, remote ischemic preconditioning (R-IPC) are methods that have been employed to reduce IRI. Aim: 1) To compare the effects of IPC and R-IPC in a rat model; 2) to investigate the clinical effect of IPC during modern liver surgery; 3) to investigate the role of the nitric oxide (NO) system in IRI, IPC and R-IPC; and 4) to explore the possible protective effects of nitrite administration before IRI. Methods: A rat model of segmental ischemia followed by 4 hours of reperfusion including microdialysis (μD) was developed from earlier models. The effects of IPC and R-IPC were compared using transaminases and histology as well as continuous μD sampling for glucose, pyruvate, lactate and glycerol. The role of the NO system was examined by serum and μD measurements of NOx as well as tissue measurements of iNOS mRNA and IL-1R mRNA. In study II, patients were randomized to IPC or no IPC prior to liver resection, where intermittent PM was used to decrease bleeding. Results: IPC was more effective in protecting the liver against IRI than R-IPC, as indicated by the levels of transaminases. Lower lactate levels were detected in patients treated with IPC before major liver resections than in controls. IPC reduced iNOS mRNA transcription during reperfusion; this result may be related to the early but not sustained increases in IL-1R transcription observed in the IPC group. Nitrite administered before ischemia reduced AST and ALT levels in the level after 4 hours of reperfusion; in addition, necrosis and glycerol release from the ischemic liver were reduced as well. Conclusion: IPC is more effective than R-IPC in animal models; however, this effect is unlikely to be of clinical importance. NOx decreases in the ischemic liver and the administration of nitrite before ischemia reduces IRI in rats. This may have clinical implications in the future.
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Karelina, Ekaterina. "MECHANISMS OF SOCIAL NEUROPROTECTION AFTER CEREBRAL ISCHEMIA." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1274922479.
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Iwase, Tomoyuki. "Ischemic Preconditioning Is Associated With a Delay in Ischemia-Induced Reduction of β-Adrenergic Signal Transduction in Rabbit Hearts". Kyoto University, 1994. http://hdl.handle.net/2433/168855.
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本文データは平成22年度国立国会図書館の学位論文(博士)のデジタル化実施により作成された画像ファイルを基にpdf変換したものである<br>Kyoto University (京都大学)<br>0048<br>新制・課程博士<br>博士(医学)<br>甲第5551号<br>医博第1521号<br>新制||医||576(附属図書館)<br>UT51-94-C9<br>京都大学大学院医学研究科内科系専攻<br>(主査)教授 北 徹, 教授 眞崎 知生, 教授 篠山 重威<br>学位規則第4条第1項該当
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Li, Ping-An. "Mechanisms of acidosis-mediated ischemic brain damage histopathology and pathophysiology /." Lund : Lund University, 1996. http://catalog.hathitrust.org/api/volumes/oclc/38158955.html.
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Ebert, Natalie Rut. "Cortical spreading ischaemia als Folge von freiem Hämoglobin und erhöhter Kaliumkonzentration im Subarachnoidalraum induziert cortikale Infakte bei der Ratte." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2001. http://dx.doi.org/10.18452/14645.
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Die Pathogenese der verzögerten ischämischen Defizite (VIND) nach Subarachnoidalblutung wird mit Produkten der Hämolyse in Zusammenhang gebracht. Topische Hirnsuperfusion mit einer artifiziellen cerebrospinalen Flüssigkeit (ACSF), die L-NA, einen NOS-Inhibitor, in Kombination mit einer erhöhten Kaliumkonzentration erhielt, hat bei der Ratte zu Ischämien geführt. Dieses Phänomen wurde als Cortical spreading ischemia (CSI) bezeichnet. Dabei scheint es während der neuronalen Depolarisation zu einer gestörten Kopplung zwischen cerebralem Metabolismus und Blutfluß zu kommen, die zu einer Vasokonstriktion und schließlich zur Ischämie führt. Die vorliegenden Arbeit beschäfftigte sich zum einen mit der Frage, ob Hämoglobin und hoch Kalium (35 mmol/l) auch zu CSIs führt,und ob es in Folge der CSIs zu cerebralen Parenchymschäden kommt. Methode: 24 Tieren wurde eine ACSF in den künstlich geschaffenen Subarachnoidalraum perfundiert. Diese ACSF enthielt eine erhöhte Kaliumkonzentration (K+ ) von 35 mmol/l und 2 mmol/l freies Hämoglobin (Hb). Unter dieser Versuchsanordnung kam es, als Antwort auf die neuronale Depolarisation, zu einem langandauernden massiven Abfall des rCBF in ischämische Bereiche, der sogenannten cortical spreading ischaemia (CSI). Zum Nachweis eines möglichen cerebralen Parenchymschadens durch die CSI wurden die Gehirne von 11 Versuchstieren histologisch untersucht. Von den 11 histologisch sowie immunhistochemisch gefärbten Hirnpräparaten wiesen 9 Hirne eine ausgeprägte cortikale Zellnekrose auf. Bei den Kontrolltieren, denen entweder nur die erhöhte K+ oder Hämoglobin in der ACSF superfundiert wurde, kam es nicht zum Auftreten von CSIs. und Anzeichen von nekrotischem Zelluntergang waren nicht zu sehen. Schlussfolge: Subarachnoidales Hb kombiniert mit hoch K+ fürt zur cortical spreading ischemia und in weiterer Folge zu ausgedehnten corticalen Infarkten.<br>The pathogenesis of delayed ischemic neurological deficits after subarachnoid hemorrhage has been related to products of hemolysis. Topical brain superfusion of artificial cerebrospinal fluid (ACSF) containing L-NA a NOS-inhibitor and high concentration of K+ has shown to induce ischemia in rats. Superimposed on a slow vasospastic reaction, the ischemic events represent spreading depolarisation of the neuronal-glial network that trigger acute vasoconstriction. The purpose of the present study was to investigate whether such spreading ischemias in the cortex could be caused also by the hemolysis products hemoglobin and K+ and whether such spreading cortical ischemias lead to brain damage. Methods: A cranial window was implanted in 24 rats. Cerebral blood flow (CBF) was measured using laser Doppler flowmetry, and direct current(DC)potentials were recorded. The ACSF was superfused topically over the brain. Rats were assigned to three groups representing ACSF composition. Analysis included classical histochemical and immunhistochemical studies. Superfusion of ACSF containing Hb combined with high concentration of K+ (35 mmol/L) reduced CBF gradually. Spreading ischemia in the cortex appeared when CBF reached 40 to 70% compared to baseline (which was 100%). This cortical spreading ischemia was characterized by sharp negative shift in DC, which preceded a steep CBF decrease that was followed by a slow recovery. In 9 of the surviving animals widespread cortical infarction was observed at the site of the cranial window and neighbouring areas in contrast to the findings in the two control groups. Conclusion: Subarachnoid Hb combined with high K+ causes cortical spreading ischemia and leads to widespread necrosis of the cortex.
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Hooshdaran, Bahman. "DUAL INHIBITION OF CATHEPSIN G AND CHYMASE AFTER ISCHEMIA REPERFUSION: THE ROLE OF INFLAMMATORY SERINE PROTEASES IN ISCHEMIA REPERFUSION INJURY." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/475423.
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Bioengineering<br>Ph.D.<br>Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality in the world (4). Restoration of coronary flow to the ischemic myocardium by interventions such as angioplasty, thrombolytic treatment or coronary bypass surgery is the current standard therapy for AMI (5). However, reperfusion of the ischemic myocardium may result in paradoxical cardiomyocyte dysfunction and worsen tissue damage, in a process known as “reperfusion injury” (6). Ischemic reperfusion (IR) injury may intensify pathological processes that contribute to the generation of oxyradicals, disturbances in cation homeostasis, and depletion of cellular energy stores, which may elicit arrhythmias, contractile dysfunction, and ultrastructural damage of the myocardium. These changes can lead to heart failure and ultimately sudden death. The exact mechanisms of IR injury are not fully known (7). Molecular, cellular, and tissue alterations such as cell death, inflammation, neurohumoral activation, and oxidat<br>Temple University--Theses
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Yusof, Mozow. "Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4779.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.<br>The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.
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SAKAMOTO, NOBUO, TATSUAKI MATSUBARA, YOSHIHIRO KAKINUMA, and TATSUO HASHIMOTO. "MYOCARDIAL METABOLIC MARKERS OF TOTAL ISCHEMIA IN VITRO." Nagoya University School of Medicine, 1994. http://hdl.handle.net/2237/15927.
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Edrissi, Hamidreza. "Blood Brain Barrier Dysfunction in Chronic Cerebral Ischemia." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32531.
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Cerebral small vessel pathology is now known to be associated with the development of cognitive impairment and mild motor impairments such as gait disturbance in a variety of neurodegenerative diseases. This dissertation explores the hypothesis that blood brain barrier dysfunction is an early event in cerebral ischemia and contributes to the development of cerebral small vessel disease (CSVD). A common rodent model of CSVD is permanent bilateral common carotid artery occlusion in the rat. This model was used to study several aspects of the progression of CSVD including the timecourse of blood brain barrier permeability changes following the onset of ischemia, gait disturbance, the expression of tight junction proteins and cytokine expression. It was determined that BBB permeability was elevated for 2 weeks following BCCAO and ischemic rats displayed lower gait velocity. There was no change in expression of TJ proteins. However, ischemic rats had higher levels of some proinflammatory cytokines and chemokines in brain tissue with no obvious changes in plasma levels.
The mechanisms underlying the increase in BBB permeability were studied in vitro using artificial barriers made of confluent rat brain microvascular endothelial cells. Cerebral ischemia has been reported to cause an increase in plasma toxicity, likely by elevating the numbers of circulating microparticles (MPs). MPs isolated from the plasma of ischemic rats were applied to artificial barriers where it was found that they act mainly as vectors of TNF-α signaling. MPs induce activation of caspase-3 and the Rho/Rho kinase pathways. It is concluded that most of the increase in barrier permeability is due to apoptosis and disassembly of actin cytoskeleton and disruption of adherens junctions IV
and not an increase in transcellular transport.
The effects of treatment with the type III phosphodiesterase inhibitor cilostazol on dye extravasation in the brain, glial activation, white matter damage and motor performance were evaluated. It was determined that cilostazol could improve the increased BBB permeability and gait disturbance and microglial activation in optic tract following BCCAO. Also, the effects of treatment with cilostazol on plasma toxicity in vivo (24h and 14d following BCCAO) and artificial barriers (in vitro) were assessed. It was found that cilostazol could reduce plasma toxicity at 24h and improve increased endothelial barrier permeability that is induced by MP treatment respectively.
In summary BBB dysfunction occurs in the rat model of chronic cerebral hypoperfusion with no differences in expression of TJ proteins. There is a mild motor disturbance in the form of lower gait velocity following BCCAO. Cytokines released in brain tissue may be associated with pathological consequences following BCCAO while there is no significant difference in plasma levels and circulating MPs may play a role in BBB dysfunction.
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Labruto, Fausto. "Modifications of cardiovascular response to ischemia and trauma /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-379-5/.
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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.
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Bogart, Robert William. "The effect of stress on global cerebral ischemia." Connect to resource, 2008. http://hdl.handle.net/1811/32235.
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Ng, Kit-ying, and 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.
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Wang, Haihui. "Ribonomic control during global brain ischemia and reperfusion." Thesis, Wayne State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3641445.
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<p> The study presented here used "omic" technology to look at the mechanism behind the selective delayed death of hippocampus CA1 neurons after transient global brain ischemia. The main findings are summarized: 1. The main form of ELAV protein family member detected in CA1/CA3 in Hu protein immunoprecipitation and polysomes was HuB (Rel-N1). HuB is present in control CA3, 8 hr reperfused CA3, and 8 hr reperfused CA1, but absent from control CA1. AUF-1, hnRNP K, hnRNP M were also absent from control CA1 following Hu protein immunoprecipitation and Western blot, suggesting that HuB bound AUF-1, hnRNP K, hnRNP M in all experimental groups except control CA1. 2. mRNA populations were different between sucrose pad preparation and sucrose gradient preparations of polysomes, although both were enriched with ARE-mRNA. This suggests different RNA binding complexes were isolated by the two methods. 3. Polysomes fractionation on sucrose pad and Hu protein immunoprecipitations using post-mitochondrial supernatants from homogenized brain regions were shown by 316 liquid chromatography mass spectroscopy to be over 75% contaminated by neuron debris, cytoskeleton and internal membrane structures, in spite of showing no contamination by Western blots of organelle markers. This suggests proteomics should become the accepted standard for validating purity of reactions derived from homogenized tissues. To summarize the results, I have worked up a consistent method of isolating polysomes from whole animal model, which has less contamination than the sucrose density gradient method. Both results from Hu IP and polysomes experiments show that control CA1 is in a different state compared with control CA3. My results suggest that the selective vulnerability of CA1 after ischemia reperfusion injury may be due, in part, to the fact that CA1 is "weaker" from the beginning. This finding is significant as it shifts the focus of research from studying the difference of ischemia reperfusion injury to the different initial states of CA1 and CA3 neurons. This study has also reformed our general idea as revealed by the high resolution of proteomics, which is superior to Western blotting for detecting contamination of samples. It is shown here that contaminationmakes up a large proportion of subcellular fractionations. This result suggests proteomics should be the new standard for quantifying contaminants, particularly in fractions obtained from whole tissues in animal experimental models.</p>
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Duarte, Sérgio Miguel Coelho. "Matrix-leukocyte interactions in liver ischemia-reperfusion injury." Doctoral thesis, Instituto de Ciências Biomédicas Abel Salazar, 2011. http://hdl.handle.net/10216/63694.
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Raghavan, Aparna. "Neuroprotective Potential of Withania Somnifera in Cerebral Ischemia." University of Toledo Health Science Campus / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=mco1416570371.
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Moore, Rustin MacArthur. "Large colon ischemia-reperfusion injury in the horse /." The Ohio State University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487853913101881.
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