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D'Addario, Vincenzo, and Capuano Pasquale. "Central Nervous System Malformations." Donald School Journal of Ultrasound in Obstetrics and Gynecology 10, no. 3 (2016): 235–55. http://dx.doi.org/10.5005/jp-journals-10009-1472.
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ABSTRACT Ultrasound (US) is a useful tool to evaluate the normal morphology, the developmental changes, and the malformations of the fetal central nervous system (CNS). The development of the fetal CNS is a complex and continuous process progressing till the end of pregnancy and even after delivery. Although, a limited number of CNS anomalies may be suspected in the 1st trimester, the 2nd trimester is the best period of pregnancy to screen for CNS anomalies, but some malformations may be recognized only in the 3rd trimester or become evident only in the postnatal period. Screening for CNS anomalies relies on the use of the basic examination, which requires two simple axial planes on the fetal head (transventricular and transcerebellar). For a more detailed evaluation of brain malformations, an expanded fetal neurosonogram is needed, based on the use of multiple sagittal and coronal planes. The correct diagnosis of a CNS anomaly must be followed by an accurate counseling since the prognosis is varying widely. How to cite this article Vincenzo D, Pasquale C. Central Nervous System Malformations. Donald School J Ultrasound Obstet Gynecol 2016;10(3):235-255.
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Spencer, P. S., G. Román, A. Buguet, A. Guekht, and J. Reis. "COVID-19: neurological sequelae." Health Risk Analysis, no. 2 (June 2021): 168–76. http://dx.doi.org/10.21668/health.risk/2021.2.16.eng.
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COVID-19, the human primarily respiratory disease caused by the coronavirus SARS-CoV-2, commonly involves the nervous system, the effects of which may persist for many months. Post-acute sequelae of COVID-19 include relapsing and remitting neurological and neuropsychiatric symptoms that can affect children and adults, including those who had mild acute illness. Since longer-term adverse effects on the central and peripheral nervous system of COVID-19 cannot be excluded, patient and societal health trends should be monitored going forward. Urgent present needs include not only global immunization against SARS-CoV-2 but also the reestablishment of lapsed mass vaccination programs to prevent resurgence of other viral diseases (e.g., measles, polio) that can impact the nervous system.
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de Boysson, H., and C. Pagnoux. "Catastrophic primary angiitis of the central nervous system." European Journal of Neurology 25, no. 1 (December 22, 2017): e3-e3. http://dx.doi.org/10.1111/ene.13469.
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Simon, Matthias, Daniel Franke, Michael Ludwig, Ales F. Aliashkevich, Gertraud Köster, Johannes Oldenburg, Azize Boström, Andreas Ziegler, and Johannes Schramm. "Association of a polymorphism of the ACVRL1 gene with sporadic arteriovenous malformations of the central nervous system." Journal of Neurosurgery 104, no. 6 (June 2006): 945–49. http://dx.doi.org/10.3171/jns.2006.104.6.945.
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Object Important central nervous system (CNS) manifestations in patients with hereditary hemorrhagic telangiectasia (HHT) include arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs). Hereditary hemorrhagic telangiectasia is caused by germline mutations of two genes: ENG (HHT Type 1) and ACVRL1 (HHT Type 2). The ENG gene variations have been associated with the formation of intracranial aneurysms. The authors studied whether sequence variations in ACVRL1 or ENG are associated with the development of clinically sporadic arteriovenous dysplasias and aneurysms of the CNS. Methods The coding sequence (in 44 patients with AVMs and 27 with aneurysms) and the 5′ end and the polyA site (in 53 patients with AVMs) of the ACVRL1 gene were analyzed for sequence variations using direct sequencing and single-strand conformational polymorphism analysis. One ENG and three ACVRL1 gene polymorphisms were genotyped using restriction enzyme–based analysis in 101 patients with sporadic AVMs and DAVFs of the CNS, 79 patients treated for intracranial aneurysms, and 202 control volunteers. The authors identified a statistically significant association between the IVS3 −35A/T polymorphism in intron 3 of the ACVRL1 gene and the development of AVMs and DAVFs (p = 0.004; odds ratio [OR] 1.73; 95% confidence interval [CI] 1.19–2.51; after adjustments for age and sex), but not aneurysms (crude OR 0.82; 95% CI 0.55–1.18). Conclusions The results of this study link ACVRL1 (HHT Type 2 gene) to the formation of the clinically sporadic variants of vascular malformations of the CNS most commonly seen in patients with HHT, that is, AVMs and DAVFs.
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Giannoccaro, Maria Pia, Sarah J. Crisp, and Angela Vincent. "Antibody-mediated central nervous system diseases." Brain and Neuroscience Advances 2 (January 2018): 239821281881749. http://dx.doi.org/10.1177/2398212818817497.
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Antibody-mediated central nervous system diseases are a relatively new area of clinical neuroscience with growing impact. Their recognition has challenged the dogma of the blood–brain barrier preventing antibody access into the central nervous system. The antibodies discovered so far are mainly against neurotransmitter receptors (e.g. N-methyl-d-aspartate and glycine receptors) and ion channel–associated proteins (leucine-rich glioma inactivated protein 1 and contactin-associated protein 2) and are expressed on the surface of neuronal synapses and elsewhere. The disorders are reversible with immunotherapies that reduce antibody levels. Although rare, the identification of these disorders in clinical practice has made central nervous system autoimmune diseases a consideration in the differential diagnoses of many clinical presentations. There is still much to learn about the aetiology of the diseases and the mechanisms by which the antibodies act, the neuronal and glial changes that follow antibody-attack, and the compensatory changes that may be required to ensure good recovery.
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Allan, Stuart M., and Nancy J. Rothwell. "Inflammation in central nervous system injury." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 358, no. 1438 (August 27, 2003): 1669–77. http://dx.doi.org/10.1098/rstb.2003.1358.
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Inflammation is a key component of host defence responses to peripheral inflammation and injury, but it is now also recognized as a major contributor to diverse, acute and chronic central nervous system (CNS) disorders. Expression of inflammatory mediators including complement, adhesion molecules, cyclooxygenase enzymes and their products and cytokines is increased in experimental and clinical neurodegenerative disease, and intervention studies in experimental animals suggest that several of these factors contribute directly to neuronal injury. Most notably, specific cytokines, such as interleukin–1 (IL–1), have been implicated heavily in acute neurodegeneration, such as stroke and head injury. In spite of their diverse presentation, common inflammatory mechanisms may contribute to many neurodegenerative disorders and in some (e.g. multiple sclerosis) inflammatory modulators are in clinical use. Inflammation may have beneficial as well as detrimental actions in the CNS, particularly in repair and recovery. Nevertheless, several anti–inflammatory targets have been identified as putative treatments for CNS disorders, initially in acute conditions, but which may also be appropriate to chronic neurodegenerative conditions.
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Zaitseva, N. V., M. A. Zemlyanova, V. N. Zvezdin, Т. I. Akafyeva, D. L. Mazunina, and А. А. Dovbish. "Effects of subchronic exposure manganese oxide nanoparticles on the central nervous system, lipid peroxidation and antioxidant enzymes in rats." Health Risk Analysis, no. 4 (April 2014): 66–77. http://dx.doi.org/10.21668/health.risk/2014.4.09.eng.
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Gonçalves, Fabrício Guimarães, and Lázaro Luis Faria do Amaral. "Constructive Interference in Steady State Imaging in the Central Nervous System." European Neurological Review 6, no. 2 (2011): 138. http://dx.doi.org/10.17925/enr.2011.06.02.138.
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Constructive interference in steady state (CISS) is a fully refocused fast-gradient echo sequence that is mainly used in the assessment of the central nervous system. The most important advantages of steady-state imaging are short acquisition times, high signal-to-noise ratio, and better contrast-to-noise ratio. Owing to its cisternographic effect, CISS is useful in the assessment of the cranial nerves, and can also be used when studying cysts, cystic masses, and neurocysticercosis and in hydrocephalus cases. CISS has been shown to be useful in spinal imaging, epecially in cases of arteriovenous malformation and when it is helpful to better characterise intra- and extramedullary cystic abnormalities.
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Hoffmann, Christine, Ute Ziegler, Anne Buschmann, Artur Weber, Leila Kupfer, Anja Oelschlegel, Baerbel Hammerschmidt, and Martin H. Groschup. "Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy." Journal of General Virology 88, no. 3 (March 1, 2007): 1048–55. http://dx.doi.org/10.1099/vir.0.82186-0.
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To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.
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Cojocaru, Inimioara, Manole Cojocaru, Isabela Silosi, and Camelia Vrabie. "Central Nervous System Manifestations in Rheumatic Diseases." Journal of Medical Biochemistry 30, no. 1 (January 1, 2011): 1–4. http://dx.doi.org/10.2478/v10011-010-0014-y.
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Central Nervous System Manifestations in Rheumatic DiseasesPatients with multi-system rheumatic conditions may have a disease affecting the central nervous system (CNS). Central nervous system manifestations vary according to the location of the lesion and range from focal findings (e.g., stroke-like presentations), although serious neurological complications in rheumatic disease appear to be rare. The most prominent features of neurological involvement in rheumatic diseases include cerebral ischaemia and psychiatric symptoms. Little information is available on the prevalence of neurological disease in patients with a rheumatological diagnosis. Involvement of the CNS may be a striking early or presenting feature with a wide variety of manifestations. There is more clarity about the CNS syndromes attributable to systemic lupus erythematosus and new insights into the central mechanisms involved in the manifestations of Sjögren's syndrome and rheumatoid arthritis. Severe CNS involvement is associated with poor prognosis, and high mortality rate. We review the spectrum of neurological diseases in patients with a rheumatological diagnosis.
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Musiek, Frank E., Teri James Bellis, and Gail D. Chermak. "Nonmodularity of the Central Auditory Nervous System." American Journal of Audiology 14, no. 2 (December 2005): 128–38. http://dx.doi.org/10.1044/1059-0889(2005/014).
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This response to A. T. Cacace and D. J. McFarland (2005) identifies points of agreement and disagreement regarding the concept of modularity in the diagnosis of (central) auditory processing disorder [(C)APD]. We concur that the evaluation of (C)APD must take into consideration the influence of higher order global or pansensory issues on performance on tests of central auditory function. To accomplish this goal, multidisciplinary (e.g., multimodal) testing is an integral part of differential diagnosis of (C)APD. We also agree that the efficiency of diagnostic tests of (C)APD should not be evaluated by imprecise criteria [e.g., "presumed" or "suspected" (C)APD], which do not provide accurate measures of the true sensitivity and specificity of these tests. Our conceptualization and recommendations for clinical practice in this area diverge, however, from that of Cacace and McFarland in a number of pivotal ways. Based on the current limitations of multimodal assessment relative to issues related to scope of practice and test efficiency, as well as the accumulated basic science and clinical literature that demonstrates the nonmodularity and interactive organization of the brain, we recommend use of the sensitized test battery of the central auditory nervous system (CANS) in combination with multidisciplinary testing to differentially diagnose (C)APD and to guide treatment of the disorder. We assert that sensitivity and specificity measures derived from individuals with well-circumscribed lesions of the CANS provide an important guide to establishing the validity of central auditory diagnostic tests. We note that researchers in the area of auditory science and (C)APD must acknowledge the challenges of the clinical arena, and we encourage their continued help to develop diagnostic tools that are both efficient and practical for the differential diagnosis of (C)APD. We conclude that our approach, which combines multidisciplinary evaluation and specific tests of central auditory function that have demonstrated sensitivity and specificity for disorders of the CANS, allows us to identify (and thus rehabilitate) the auditory deficits present in individuals with (C)APD in its "purest" form. It also permits the identification and rehabilitation of auditory deficits in individuals who exhibit auditory perceptual problems that coexist with other processing problems, while ruling out those who perform poorly on auditory tests because of a global, supramodal problem involving cognition, attention, language, memory, or related skills.
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Liu, Xinhuai, and Allan E. Herbison. "Kisspeptin Regulation of Neuronal Activity throughout the Central Nervous System." Endocrinology and Metabolism 31, no. 2 (2016): 193. http://dx.doi.org/10.3803/enm.2016.31.2.193.
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Reuck, Jacques L. De. "Cortical Superficial Siderosis of the Central Nervous System – An Overview." European Neurological Review 9, no. 1 (2014): 68. http://dx.doi.org/10.17925/enr.2014.09.01.68.
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Cortical superficial siderosis (cSS) is observed on gradient echo T2*-weighted magnetic resonance imaging (MRI) as a hypo-intensity outlining the convexity of the cerebral hemispheres. It is composed of haemosiderin deposits in the subpial space. It was initially thought to be a rare condition but with 7.0 Tesla (T) MRI it appears to be not uncommon. Its symptomatology depends on the underlying cortical pathology. Diffuse cSS is mainly related to the sequels of an underlying lobar haematoma, mainly due to cerebral amyloid angiopathy (CAA). Focal cSS is more due to cortical microinfarcts, that underwent haemorrhagic transformation, rather than due to cortical microbleeds. cSS is not only found in patients suffering from CAA but also in those suffering from several neurodegenerative dementia syndromes and after cerebral trauma.
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Finsterer, J., and H. Auer. "Parasitoses of the human central nervous system." Journal of Helminthology 87, no. 3 (October 10, 2012): 257–70. http://dx.doi.org/10.1017/s0022149x12000600.
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AbstractCerebral involvement in parasitoses is an important clinical manifestation of most of the human parasitoses. Parasites that have been described to affect the central nervous system (CNS), either as the dominant or as a collateral feature, include cestodes (Taenia solium (neurocysticerciasis), Echinococcus granulosus (cerebral cystic echinococcosis), E. multilocularis (cerebral alveolar echinococcosis), Spirometra mansoni (neurosparganosis)), nematodes (Toxocara canis and T. cati (neurotoxocariasis), Trichinella spiralis (neurotrichinelliasis), Angiostrongylus cantonensis and A. costaricensis (neuroangiostrongyliasis), Gnathostoma spinigerum (gnathostomiasis)), trematodes (Schistosoma mansoni (cerebral bilharziosis), Paragonimus westermani (neuroparagonimiasis)), or protozoa (Toxoplasma gondii (neurotoxoplasmosis), Acanthamoeba spp. or Balamuthia mandrillaris (granulomatous amoebic encephalitis), Naegleria (primary amoebic meningo-encephalitis), Entamoeba histolytica (brain abscess), Plasmodium falciparum (cerebral malaria), Trypanosoma brucei gambiense/rhodesiense (sleeping sickness) or Trypanosoma cruzi (cerebral Chagas disease)). Adults or larvae of helminths or protozoa enter the CNS and cause meningitis, encephalitis, ventriculitis, myelitis, ischaemic stroke, bleeding, venous thrombosis or cerebral abscess, clinically manifesting as headache, epilepsy, weakness, cognitive decline, impaired consciousness, confusion, coma or focal neurological deficits. Diagnosis of cerebral parasitoses is dependent on the causative agent. Available diagnostic tools include clinical presentation, blood tests (eosinophilia, plasmodia in blood smear, antibodies against the parasite), cerebrospinal fluid (CSF) investigations, imaging findings and occasionally cerebral biopsy. Treatment relies on drugs and sometimes surgery. Outcome of cerebral parasitoses is highly variable, depending on the effect of drugs, whether they are self-limiting (e.g. Angiostrongylus costaricensis) or whether they remain undetected or asymptomatic, like 25% of neurocysticerciasis cases.
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Basmajian, John V. "A Glorious Symphony: Muscles-Ligaments-Central Nervous System." Journal of Sport and Exercise Psychology 19, s1 (January 1997): S126—S130. http://dx.doi.org/10.1123/jsep.19.s1.s126.
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In the symphony of neuromotor performance, the muscles are the powerful woodwinds, the ligaments are the essential string section, and the central nervous system both writes and conducts the performance. Electromyography (EMG) has provided the platform and technology in the past half century to bring appreciation of the superb functions of all the parts of the healthy body in concert. This broad “review” provides vignettes of many aspects of motor controls in the upper and lower limbs explored with EMG by the author and his students.
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Belyaeva, V. A. "Stress before exams as a risk factor causing functional disorders in the cardiovascular system in students with different metabolic status." Health Risk Analysis, no. 4 (December 2020): 147–55. http://dx.doi.org/10.21668/health.risk/2020.4.17.eng.
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Students who attend a medical HEE often face strain in their adaptation mechanisms when preparing for exams; it can create substantial preconditions for functional deregulation in body systems. The articles outlines some results obtained via examining heart rate variability (HRV) in students of the 2nd and the 3rd year attending the North Ossetia State Medical Academy who had different metabolic status in a period prior to exams. Our research goal was to assess the state of the vegetative nervous system and regulatory systems in students with different metabolic status (BMI< 25; BMI=25–29.99; BMI=30–34.99.) who had to face excess stress during preparation to exams. Heart rate intervals were registered during five minutes in an examined person being at rest. HRV parameters were analyzed in time and frequency domains. We revealed that medical students had elevated activity of the sympathetic section in their vegetative nervous system (VNS) during a period prior to exams; in particular, it was apparent for the regulation system of the vasomotor center (PLF = 48.4%). Students’ bodies had apparent strain in their regulatory systems (SI=177.5 a.u.). Total activity of the regulatory system was significantly elevated (TP=2,293 msec2) due to central regulation levels. As students’ BMI grew, there was a decrease in activity of the parasympathetic component in vegetative regulation and heart rate management became more centralized (IC=3.2–4.5 a.u.). Students with Class 3 obesity had the maximum spectrum power of the superlow component in heart rate variability (PVLF=29.3%). HRV parameters analysis allows estimating whether adaptation processes in students’ bodies are adequate during preparation to exams; it can be done in screening mode and provides an opportunity to perform timely prevention activities.
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Belyaeva, V. A. "Stress before exams as a risk factor causing functional disorders in the cardiovascular system in students with different metabolic status." Health Risk Analysis, no. 4 (December 2020): 147–55. http://dx.doi.org/10.21668/health.risk/2020.4.17.eng.
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Students who attend a medical HEE often face strain in their adaptation mechanisms when preparing for exams; it can create substantial preconditions for functional deregulation in body systems. The articles outlines some results obtained via examining heart rate variability (HRV) in students of the 2nd and the 3rd year attending the North Ossetia State Medical Academy who had different metabolic status in a period prior to exams. Our research goal was to assess the state of the vegetative nervous system and regulatory systems in students with different metabolic status (BMI< 25; BMI=25–29.99; BMI=30–34.99.) who had to face excess stress during preparation to exams. Heart rate intervals were registered during five minutes in an examined person being at rest. HRV parameters were analyzed in time and frequency domains. We revealed that medical students had elevated activity of the sympathetic section in their vegetative nervous system (VNS) during a period prior to exams; in particular, it was apparent for the regulation system of the vasomotor center (PLF = 48.4%). Students’ bodies had apparent strain in their regulatory systems (SI=177.5 a.u.). Total activity of the regulatory system was significantly elevated (TP=2,293 msec2) due to central regulation levels. As students’ BMI grew, there was a decrease in activity of the parasympathetic component in vegetative regulation and heart rate management became more centralized (IC=3.2–4.5 a.u.). Students with Class 3 obesity had the maximum spectrum power of the superlow component in heart rate variability (PVLF=29.3%). HRV parameters analysis allows estimating whether adaptation processes in students’ bodies are adequate during preparation to exams; it can be done in screening mode and provides an opportunity to perform timely prevention activities.
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Campos, Patrícia, Guillermo Cruz, Rodolfo Lizarraga, Ernesto Bancalari, Daniel Guillen, and Carlos Castañeda. "Electroencephalography in congenital malformations of the central nervous system." Arquivos de Neuro-Psiquiatria 52, no. 4 (December 1994): 515–22. http://dx.doi.org/10.1590/s0004-282x1994000400010.
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We studied clinical and EEG features of 36 cases with congenital malformations of the CNS. Patients were followed at the outpatient clinic of Hospital Cayetano Heredia and of Hogar Clinica San Juan de Dios in Lima-Peru, from January 1984 to June 1992. Eighty percent of the patients had convulsive syndromes and mental retardation. The most frequent malformation was agenesis of corpus callosum, and it was not possible to find a "typical" EEG pattern. The second were porencephalic cysts, with a good clinical-EEG correlation. There were two typical cases of schizencephaly, one of hemimegalencephaly with good prognosis, and one of holoprosencephaly. The results are compared to those obtained for a series we previously reported. Data discussed take into account reports on the subject registered in the literature. It is concluded that EEG is an useful method to evaluate possible CNS malformations in developing countries.
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Vandebroek, Arno, and Masato Yasui. "Regulation of AQP4 in the Central Nervous System." International Journal of Molecular Sciences 21, no. 5 (February 26, 2020): 1603. http://dx.doi.org/10.3390/ijms21051603.
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Aquaporin-4 (AQP4) is the main water channel protein expressed in the central nervous system (CNS). AQP4 is densely expressed in astrocyte end-feet, and is an important factor in CNS water and potassium homeostasis. Changes in AQP4 activity and expression have been implicated in several CNS disorders, including (but not limited to) epilepsy, edema, stroke, and glioblastoma. For this reason, many studies have been done to understand the various ways in which AQP4 is regulated endogenously, and could be regulated pharmaceutically. In particular, four regulatory methods have been thoroughly studied; regulation of gene expression via microRNAs, regulation of AQP4 channel gating/trafficking via phosphorylation, regulation of water permeability using heavy metal ions, and regulation of water permeability using small molecule inhibitors. A major challenge when studying AQP4 regulation is inter-method variability. A compound or phosphorylation which shows an inhibitory effect in vitro may show no effect in a different in vitro method, or even show an increase in AQP4 expression in vivo. Although a large amount of variability exists between in vitro methods, some microRNAs, heavy metal ions, and two small molecule inhibitors, acetazolamide and TGN-020, have shown promise in the field of AQP4 regulation.
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Neubauer, Judith A., and Jagadeeshan Sunderram. "Oxygen-sensing neurons in the central nervous system." Journal of Applied Physiology 96, no. 1 (January 2004): 367–74. http://dx.doi.org/10.1152/japplphysiol.00831.2003.
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This mini-review summarizes the present knowledge regarding central oxygen-chemosensitive sites with special emphasis on their function in regulating changes in cardiovascular and respiratory responses. These oxygen-chemosensitive sites are distributed throughout the brain stem from the thalamus to the medulla and may form an oxygen-chemosensitive network. The ultimate effect on respiratory or sympathetic activity presumably depends on the specific neural projections from each of these brain stem oxygen-sensitive regions as well as on the developmental age of the animal. Little is known regarding the cellular mechanisms involved in the chemotransduction process of the central oxygen sensors. The limited information available suggests some conservation of mechanisms used by other oxygen-sensing systems, e.g., carotid body glomus cells and pulmonary vascular smooth muscle cells. However, major gaps exist in our understanding of the specific ion channels and oxygen sensors required for transducing central hypoxia by these central oxygen-sensitive neurons. Adaptation of these central oxygen-sensitive neurons during chronic or intermittent hypoxia likely contributes to responses in both physiological conditions (ascent to high altitude, hypoxic conditioning) and clinical conditions (heart failure, chronic obstructive pulmonary disease, obstructive sleep apnea syndrome, hypoventilation syndromes). This review underscores the lack of knowledge about central oxygen chemosensors and highlights real opportunities for future research.
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Rock, R. Bryan, Genya Gekker, Shuxian Hu, Wen S. Sheng, Maxim Cheeran, James R. Lokensgard, and Phillip K. Peterson. "Role of Microglia in Central Nervous System Infections." Clinical Microbiology Reviews 17, no. 4 (October 2004): 942–64. http://dx.doi.org/10.1128/cmr.17.4.942-964.2004.
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SUMMARY The nature of microglia fascinated many prominent researchers in the 19th and early 20th centuries, and in a classic treatise in 1932, Pio del Rio-Hortega formulated a number of concepts regarding the function of these resident macrophages of the brain parenchyma that remain relevant to this day. However, a renaissance of interest in microglia occurred toward the end of the 20th century, fueled by the recognition of their role in neuropathogenesis of infectious agents, such as human immunodeficiency virus type 1, and by what appears to be their participation in other neurodegenerative and neuroinflammatory disorders. During the same period, insights into the physiological and pathological properties of microglia were gained from in vivo and in vitro studies of neurotropic viruses, bacteria, fungi, parasites, and prions, which are reviewed in this article. New concepts that have emerged from these studies include the importance of cytokines and chemokines produced by activated microglia in neurodegenerative and neuroprotective processes and the elegant but astonishingly complex interactions between microglia, astrocytes, lymphocytes, and neurons that underlie these processes. It is proposed that an enhanced understanding of microglia will yield improved therapies of central nervous system infections, since such therapies are, by and large, sorely needed.
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Strati, Paolo, Joon Uhm, Timothy Kaufmann, Sameer A. Parikh, Curtis A. Hanson, Kari Chaffee, Sara Achenbach, Timothy G. Call, and Tait D. Shanafelt. "Central Nervous System Involvement By Chronic Lymphocytic Leukemia." Blood 126, no. 23 (December 3, 2015): 2919. http://dx.doi.org/10.1182/blood.v126.23.2919.2919.
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Abstract INTRODUCTION. Although uncommon, involvement of the central nervous system (CNS) is the most common extramedullary manifestation of Chronic Lymphocytic Leukemia (CLL). Nonetheless, a broad array of conditions can lead to neurologic symptoms in CLL patients and distinguishing between clinically significant CLL involvement of the CNS and other etiologies can be challenging. The actual prevalence of CNS involvement by CLL is unknown, the only available data being case reports and small case series. METHODS. Between 01/1995 and 11/2014, 186 of the 4317 (4%) patients with CLL followed at our center underwent an MRI of the CNS (e.g. brain, spine) and/or a lumbar puncture (LP) with cerebral spinal fluid (CSF) analysis to evaluate neurologic symptoms. As the mere presence of CLL cells in the CSF is not diagnostic of clinically significant CNS disease, a final diagnosis of clinically significant CNS involvement by CLL was established by the collaborative review of the pathologist, neurologist and treating hematologist based on comprehensive work-up and multi-disciplinary evaluation. RESULTS. After evaluation, the etiology of neurologic symptoms was clinically significant involvement of the CNS by CLL in 19 (10%) patients, CNS Richter Syndrome (RS) in 15 (8%), infection in 42 (23%), autoimmune conditions in 31 (17%), other cancer in 9 (5%), and another etiology in 70 (37%). The sensitivity of LP to detect clinically significant CNS involvement by CLL was 89%, however its specificity was only 42% where CLL cells were also frequently observed in the CSF in concomitance with inflammatory processes, such as infections and autoimmune disease. Factors associated with clinically significant CNS involvement by CLL/RS were mutated IGHV (p=0.04), low CSF glucose (p=0.02), elevated CSF total nucleated cells (TNC)(p=0.004), lymphocytes (p=0.02) and CLL cells, both as absolute count (p=0.05) and percentage of TNC (p=0.02). Median OS among patients with clinically significant CNS involvement by CLL or RS were 21 and 11 months, respectively. Median OS for patients with neurological symptoms secondary to infection was 6 months, to autoimmune process was 63 months, to other cancers was 19 months, and to other non-CLL related etiologies was 37 months. CONCLUSIONS. Clinically significant CNS involvement by CLL and RS are rare conditions. Neurologic symptoms in patients with CLL are attributable to non-CLL-related etiologies in the majority of cases, even when CLL B-cells are present in the CSF. Analysis of the CSF has high sensitivity but limited specificity to distinguish clinically significant CNS involvement by CLL from other etiologies. Comprehensive evaluation is required before attributing neurologic symptoms to CLL. Disclosures No relevant conflicts of interest to declare.
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Halperin, J. J. "Oral treatment of parenchymal central nervous system neuroborreliosis - are we there yet?" European Journal of Neurology 21, no. 9 (April 8, 2014): 1147–48. http://dx.doi.org/10.1111/ene.12440.
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Keddie, S., V. Bharambe, A. Jayakumar, A. Shah, V. Sanchez, A. Adams, and S. Gnanapavan. "Clinical perspectives into the use of thalidomide for central nervous system tuberculosis." European Journal of Neurology 25, no. 11 (July 18, 2018): 1345–51. http://dx.doi.org/10.1111/ene.13732.
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Gioia, Laura, Alexandre Y. Poppe, and Sylvain Lanthier. "Primary Angiitis of the Central Nervous System - Clinical Approaches, Challenges and Controversies." European Neurological Review 6, no. 3 (2011): 181. http://dx.doi.org/10.17925/enr.2011.06.03.181.
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Primary angiitis of the central nervous system (PACNS) is a rare and life-threatening form of vasculitis confined to the CNS. A timely diagnosis is a real challenge because clinical manifestations of PACNS are diverse and nonspecific. Headaches, cerebrospinal fluid inflammation and abnormal brain magnetic resonance imaging are prevalent. When PACNS is suspected, a thorough investigation is mandatory to rule out several potential simulators and confirm the diagnosis. Treatment of PACNS is also a challenge involving competing forces, which include the threat of serious adverse effects of potent immunosuppressive agents and the risk of neurological deteriorations due to insufficient immunosuppressant therapy. Efforts are ongoing to delineate subtypes requiring different therapeutic approaches and having distinct prognoses. Despite recent progress, PACNS is still fatal in as much as one-sixth of cases. Long-term follow-up is mandatory in patients with PACNS.
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Malessy, Martijn J. A., Ralph T. W. M. Thomeer, and J. Gert van Dijk. "Changing central nervous system control following intercostal nerve transfer." Journal of Neurosurgery 89, no. 4 (October 1998): 568–74. http://dx.doi.org/10.3171/jns.1998.89.4.0568.
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Object. The goal of this study was to find which central nervous system (CNS) pathways are involved in volitional control over reinnervated biceps or pectoral muscles. Methods. Intercostal nerves (ICNs) were coapted to the musculocutaneous nerve (MCN) or the medial pectoral nerve (MPN) in 23 patients with root avulsions of the brachial plexus to restore biceps or pectoral muscle function. The facilitatory effects of respiration and voluntary contraction on cortical motor-evoked potentials of biceps or pectoral muscles were used to study CNS control over the reinnervated muscles. The time course of the facilitatory effect of respiration and voluntary contraction differed significantly. In the end stage of nerve regeneration, the facilitatory effect of voluntary contraction was significantly larger than that of respiration, indicating that the CNS control network over the muscle comes to resemble that of the recipient nerve (MCN or MPN) rather than that of the donor nerve (ICN). Conclusions. The strengthening of previously subthreshold synaptic connections in a CNS network connecting ICN to MCN or MPN neurons may underlie changing excitability.
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Girard, Sophie, Thérèse Couderc, Josette Destombes, Danièle Thiesson, Francis Delpeyroux, and Bruno Blondel. "Poliovirus Induces Apoptosis in the Mouse Central Nervous System." Journal of Virology 73, no. 7 (July 1, 1999): 6066–72. http://dx.doi.org/10.1128/jvi.73.7.6066-6072.1999.
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ABSTRACT Poliovirus (PV) is the etiological agent of human paralytic poliomyelitis. Paralysis results from the destruction of motoneurons, a consequence of PV replication. However, the PV-induced process leading to the death of motoneurons is not well known. We investigated whether PV-induced central nervous system (CNS) injury is associated with apoptosis by using mice as animal models. Transgenic mice expressing the human PV receptor were infected intracerebrally with either the neurovirulent PV-1 Mahoney strain or a paralytogenic dose of the attenuated PV-1 Sabin strain. Nontransgenic mice were infected with a mouse-adapted PV-1 Mahoney mutant. DNA fragmentation was demonstrated in CNS tissue from paralyzed mice by visualization of DNA oligonucleosomal laddering and by enzyme-linked immunosorbent assay. Viral antigens and DNA fragmentation detected by the in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling technique were colocalized in neurons of spinal cords from paralyzed mice. In addition, morphological changes characteristic of cells undergoing apoptosis were observed in motoneurons by electron microscopy. Thus, we show that PV multiplication and CNS injury during paralytic poliomyelitis are associated with apoptosis.
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Fontes, H., H. Nzwalo, S. Mendes, S. Fernandes, G. Ponte, and M. Pereira. "Central nervous system vasculitis presenting as acute psychotic disorder." European Psychiatry 26, S2 (March 2011): 745. http://dx.doi.org/10.1016/s0924-9338(11)72450-6.
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IntroductionAcute psychosis can represent a diagnosis challenge. Several disorders can be implicated, and some representing a life threatening condition. We report a rare case of acute psychosis with persistent soft neurological signs as a primary presentation of a central nervous system vasculitis.ResultsA 23 year old man, with antecedent of depression, previous history of cocaine and marijuana abuse, admitted to an acute psychiatric ward with three days evolution of disturbed behavior, mainly isolation and immobility. On the psychiatric ward he appeared vague, with negativism, inattentiveness, and elementary and incoherent speech. He had unsystematised delusions. His neurological examination revealed a slight ataxic gait and discoordination, and signs of frontal lobe release. Initial extensive complementary study, including brain CT, EEG, and urine toxicology were negative. He began treatment with risperidone and clomipramine, with improvement of his mental condition, and by the second week he was able maintain a coherent speech. The neurological signs did not improve, and frequent falls appeared. We performed a brain MRI who revealed lesions compatible with vasculitis. The extensive liquor study was negative, with exception of proteins levels (56 md/dl). He was transferred to an internal medicine ward, treated with corticoesteroid. His condition improved in the following weeks and on discharge from Hospital he had recovered his mental status and was autonomous.ConclusionsPsychosis is an uncommon presentation of central nervous system vasculitis. In cases of persistence or progression of the soft neurological signs, further complementary study is essential to exclude organic pathology.
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Bahadoran, Philippe, Robert Ballotti, and Jean-Paul Ortonne. "Hypomelanosis, immunity, central nervous system: No more ?and?, not the end." American Journal of Medical Genetics 116A, no. 4 (January 9, 2003): 334–37. http://dx.doi.org/10.1002/ajmg.a.10066.
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Savino, Angela Maria, Orianne Olivares, Shani Barel, Lev Yakimov, Ifat Geron, Hila Fishman, Inbal Mor, et al. "Stearoyl-CoA Desaturase (SCD) Enhances Central Nervous System Leukemia." Blood 132, Supplement 1 (November 29, 2018): 389. http://dx.doi.org/10.1182/blood-2018-99-114749.
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Abstract Background: Central nervous system (CNS) involvement by acute lymphoblastic leukemia (ALL) is a major clinical concern. Leukemic cells can be found in the CNS at diagnosis (1-2%) or, more frequently, at relapse (30%). Very little is known about the pathogenesis and therefore there are no targeted therapies. Prophylactic CNS-directed conventional intrathecal chemotherapy or irradiation are required for relapse-free survival. However, they are associated with substantial rates of short and long term toxicity. Therefore, elucidation of molecular mechanisms and pathways mediating leukemia-cell entry and survival in the CNS is needed to develop alternative CNS-directed treatment strategies. Previous studies showed an increased expression of Stearoyl-CoA desaturase (SCD), a key enzyme of the de novo fatty acid synthesis pathway, in B cell precursor (BCP) ALL cells isolated from cerebrospinal fluid (CSF) of patients at the time of CNS relapse. A small SCD positive population was detected in the bone marrow (BM) at leukemia diagnosis in patients who later developed isolated CNS relapse, defining a potential biomarker for CNS relapse. It is unknown, however, if SCD has a functional role in CNS leukemia. Aim: To examine the hypothesis that increased expression of SCD enhances trafficking and survival of human B-ALL cells in the CNS Methods: We analyzed leukemia-cell entry into the CNS using xenografts of human BCP-ALL cell lines. Microarray profile of cells isolated from CNS and BM of transplanted mice was performed. Cell lines were transduced to overexpress human SCD and evaluated in vitro for proliferation kinetics and metabolic SCD activity. In vivo, SCD overexpressing cells were transplanted in NSG mice,sacrificed upon the first symptoms of CNS involvement, e.g. hind limb paralysis. BM, spleen and meninges were collected and analyzed to check human engraftment by FACS. The tumor load was expressed as total amount of leukemic cells in each organ. Competition assays were performed by transplanting SCD overexpressing and WT cells in the same mouse in a 1:1 ratio. Results: BCP-ALL cells transplanted into NSG mice faithfully recapitulated pathological features of meningeal infiltration seen in patients with ALL. Gene expression analysis of cells collected from BM and meninges of leukemic mice revealed up-regulation of the genes belonging to the signaling pathway of sterol regulatory element binding proteins (SREBPs) in ALL cells isolated from the CNS. SCD, whose transcription is controlled by the SREBP family, was significantly upregulated. SCD overexpression did not alter proliferation in vitro. Since SCD introduces a double bond in Stearoyl-CoA, its activity was measured as the ratio of unsaturated/saturated fatty acids in the cells. That ratio was increased in SCD overexpressing cells in vitro, confirming the functionality of the enzyme. In vivo, mice transplanted with SCD overexpressing cells led to a faster onset of CNS disease manifested by a clinical phenotype of earlier hind limb paralysis compared to control and significant increased number of leukemic cells in the CNS (Figure 1A).SCD overexpression also induced CNS engraftment of another B-ALL cell line, REH, which is not naturally prone to invade the central nervous system. Mice transplanted with SCD overexpressing REH cells showed the same phenotype of earlier hind limb paralysis and accumulation of leukemic cells in the CNS as the CNS-prone 018z cells, while WT REH did not show any CNS engraftment but comparable tumor load in BM and spleen (Figure1B). To reproduce the clonal heterogeneity in SCD expression observed previously in patients' BM, we performed a competition assay transplanting SCD overexpressing cells and control cells, expressing different fluorochromes, in the same mouse in a 1:1 ratio. In the CNS, the ratio between SCD overexpressing and WT cells ranged from 2 to 20 fold. This effect was unique to the CNS and not reproducible in the other hematopoietic organs where the 1:1 ratio was maintained (Figure 1C). Moreover, SCD overexpression sensitized leukemic cells to mTOR inhibitors, suggesting a potential therapeutic option Conclusion: SCD has a role in homing and survival of leukemic cells in the CNS and may be used as early predictor of CNS relapse. This study reveals a role for SCD and fatty acid metabolism in the pathogenesis of CNS leukemia suggesting that this pathway maybe targeted for specific therapy of this devastating disease. Figure 1. Figure 1. Disclosures Halsey: Jazz Pharmaceuticals: Honoraria, Other: Support for conference attendance.
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Pouzoulet, Frederic, Keyvan Rezai, Zhimin Li, Qiu Yushi, Han W. Tun, Dalila Labiod, Sarah Bonnet-Boissinot, and Carole Soussain. "Preclinical Evaluation of Ibrutinib for Central Nervous System Lymphoma." Blood 128, no. 22 (December 2, 2016): 4170. http://dx.doi.org/10.1182/blood.v128.22.4170.4170.
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Abstract Introduction Primary CNS lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL), predominantly of non-germinal center (non-GC) subtype. Currently available treatments remain disappointed with a non-optimal complete remission rate and a high relapse rate. As such, novel therapeutic agents are urgently needed. Constitutive activation of the NF-kB pathway via mutations in B cell receptor (BCR) (CD79B) and mutation of MYD 88 and TBL1XR1 pathways plays an important role in PCNSL. Ibrutinib, an inhibitor of BCR signaling, has been found to have significant therapeutic activity in relapsed or refractory non-CNS non-GC DLBCL that display similar NFKB mutational patterns. We have performed a CNS pharmacokinetic (PK) study of Ibrutinib and evaluated its therapeutic activity against CNS lymphoma (CNSL) in murine models. Methods CNS PK study in mice - The first study was done in a CNSL model created by intracerebral implantation of luciferase-transfected lymphoma cells (MC116) in nude mice in comparison to healthy nude mice without lymphoma cell implantation (N=5 per group). Once the tumor activity was confirmed by bioluminescence imaging in CNSL group, all the mice were treated with ibrutinib 12 or 30 mg/kg/day by oral gavage (OG) for 5 days. Blood and brain were collected 2 hours after the last dose. Ibrutinib was measured by ultra performance liquid chromatography with tandem mass spectrometry. Cerebro-spinal fluid (CSF) PK study in Sprague-Dawley (SD) rats - Ibrutinib 50 mg/kg single dose was given by OG (N=6). Microdialysates of CSF were collected from a ventricle of the brain and a carotid artery via microdialysis catheters every hour for 13 hours post-treatment. Drug concentrations were determined by capillary electrophoresis with laser detection. Preclinical therapeutic evaluation - A murine CNS lymphoma model was created by intracerebral injection of the OCI-Ly10 non-GC DLBCL cells, which were confirmed to have CD79 A and MYD 88 mutations and show high sensitivity to Ibrutinib in vitro. Animals were sacrificed if they showed severe clinical signs or symptoms or >20% weight loss. Ibrutinib 30 mg/kg was administered by OG daily starting at day 7 post-implantation and until the last sacrifice in the control group treated with vehicle. Therapeutic efficacy was determined by Kaplan-Meier survival analysis using date of sacrifice as endpoint. Results CNS PK study in mice - 1) Ibrutinib levels in plasma, normal brain tissue and brain-tumor were analyzed. Ibrutinib was not detected in healthy control mice treated with vehicle. In healthy mice treated with ibrutinib (12 mg/kg and 30 mg/kg), Ibrutinib mean plasmatic levels were 9.31 (±3.56) ng/mL and 42.2 (±20.9) ng/mL respectively. At 12 mg/kg dose level, ibrutinib was detectable but not quantifiable in brain tissue. After treatment with 30 mg/kg,iIbrutinib mean levels were 0.0077 (±0.0053) and 0.0071 (±0.00483) ng/g tissue in right and left cerebral hemispheres respectively. In CNSL mice treated with ibrutinib (12 mg/kg and 30 mg/kg), Ibrutinib mean plasmatic levels were 12.03 (±9.04) ng/mL and 42.64 (±42.04) ng/mL respectively, brain ibrutinib levels were 0.008 (±0.005) and 0.007 (±0.003) ng/g tissue for tumor-bearing right hemisphere and non-tumor bearing left hemisphere respectively for 30 mg/kg, while brain ibrutinib level was detectable but not quantifiable at 12mg/kg. CSF PK study in SD rats - CSF penetration of ibrutinib was determined to be ~5.2 % as calculated by area under the curve (AUC) ratio of CSF and blood samples. Cmax in CSF is ~0.35 uM, which is significantly higher than published EC50 concentrations for DLBCL cell lines. Preclinical therapeutic evaluation -Ibrutinib showed an excellent therapeutic activity with significant prolongation of survival (p=0.0137) (fig 1). At a median follow-up of 112 days, the median survival in treated CNSL group is 56 days compared to 33 days in the control group. At the end of the follow-up 33% of animals in treated CNSL group are still alive without treatment. Conclusion Ibrutinib achieves high concentrations in brain and CSF in murine CNS PK models with promising single-agent preclinical therapeutic activity against CNS lymphoma in a murine model. Further studies to develop combination regimen are ongoing. Figure Figure. Disclosures Soussain: Roche: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding.
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Cote, Gregory M., Yang Feng, Aliyah R. Sohani, Zachary J. Roberts, Anna Colpo, Fred H. Hochberg, Yi-Bin A. Chen, et al. "Secondary Central Nervous System Lymphoma: A Single Center Experience." Blood 118, no. 21 (November 18, 2011): 5181. http://dx.doi.org/10.1182/blood.v118.21.5181.5181.
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Abstract Abstract 5181 Background: Secondary CNS non-Hodgkin lymphoma (SCNSL) is estimated to occur in ∼5% of patients with non-Hodgkin lymphoma, and it carries a poor prognosis. Early CNS relapse (i.e. during treatment or within the first 6 months following chemotherapy) may represent subclinical CNS lymphoma present at the time of diagnosis. DLBCL is the most common histology seen in SCNSL and primary CNS (PCNSL) lymphoma. PCNSL DLBCL is usually characterized by an activated B-cell like (ABC) phenotype; it is unknown whether SCNSL follows the same pattern or if it includes germinal center B-cell (GCB) and non-ABC/non-GCB phenotypes. Methods: We queried our IRB approved clinicopathologic database of hematologic malignancies for patients with lymphoma diagnosed between 1999 and July 2011 who had brain or spine MRI, head CT, lumbar puncture or intrathecal chemotherapy. Clinical data and patient characteristics were extracted. We also obtained pathologic features of tumors including immunohistochemistry and cytogenetics, when available. Descriptive statistics were used to characterize patients at baseline. Overall survival (OS) is defined as the time from time from systemic lymphoma diagnosis (i.e. disease outside of the CNS) to death (event), or censored at last known date of survival. Overall survival curves were obtained using the Kaplan-Meier method with 95% confidence intervals calculated using Greenwood's formula. We did an analysis of CNS lymphoma diagnosis within the first 6 months from systemic lymphoma diagnosis (Early CNS involvement) versus greater than 6 months from systemic lymphoma diagnosis (Late CNS relapse), based on Multivariable logistic regression. The associations between potential risk factors and OS after CNS relapse have been explored using the stepwise Cox regression models. Results: One-hundred and twelve patients met the criteria of systemic lymphoma with CNS relapse/involvement with 68% DLBCL and the remainder including Mantle Cell lymphoma (5%), BL (5%), CLL/SLL (4%) and others. Of the DLBCL patients, 25/76 (33%) were GCB type, 20/76 (26%) were non-GCB, and the remaining unclassifiable with the data available. The median OS for all patients was 23 mo (95% CI=11–41), and 6.7 mo (95% CI=4.6–9.9) after CNS lymphoma diagnosis. Sixty-one of 112 patients (54%) were found to have CNS lymphoma within 6 mo of systemic lymphoma diagnosis including 40 patients (36%) where CNS involvement was present at the time of, or within the first month of, systemic diagnosis, suggesting that these are concurrent presentations. Median OS for patients with early (i.e. concurrent systemic and CNS lymphoma and early CNS relapse patients) v. late CNS relapse was 8.5 mo (95% CI=5.5–10.4) compared to 57.8 mo (95% CI=33.2–94.7), (p < 0.003). The OS after CNS diagnosis was similar between the two groups at 5.5 mo (95% CI=2.85–11) and 8.2 mo (95% CI=3.9–9.7), respectively (p=0.5). Regression analysis of clinical and pathological features (e.g. age, sex, stage, IPI score, LDH, histology, cytogenetics, immunohistochemistry, initial treatment and others) was performed to determine if there were factors associated with early versus late CNS lymphoma involvement and none were significant or clinically relevant. Hazard ratios (HR) for OS after CNS relapse favored patients who obtained a CNS complete response (CR1, HR=0.18, p=<0.01, 95% CI=0.08–0.40) or partial response (PR1, HR=0.31, p=0.004, 95% CI=0.14–0.68). Fifteen patients underwent autologous stem cell transplantation (ASCT) for CNS lymphoma therapy; the median OS after CNS relapse was over 1000 days (HR=0.19, p=0.002, 95% CI=0.07–0.56), suggesting a benefit for intensive therapy in selected patients. HR's for OS after CNS relapse were worse for DLBCL patients with non-GCB phenotype (HR=5.61, 95% CI=2.85–11) and those with an elevated LDH and >1 site of EN disease (HR=2.50, p=0.004, 95% CI=1.34–4.68) at the time of systemic diagnosis, perhaps reflecting more aggressive disease at initial presentation. Conclusion: The prognosis of secondary CNS lymphoma remains poor, though selected patients who undergo high-dose chemotherapy with ASCT may enjoy prolonged remissions. In contrast to PCNSL, both GCB and non-GCB DLBCL relapse in the CNS, with the non-GCB subtype associated with an inferior prognosis. For patients at high-risk of CNS involvement, efforts must be directed at prophylactic strategies and novel therapeutic approaches. Disclosures: No relevant conflicts of interest to declare.
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Ojeda, Jorge, Ariel Ávila, and Pía M. Vidal. "Gut Microbiota Interaction with the Central Nervous System throughout Life." Journal of Clinical Medicine 10, no. 6 (March 21, 2021): 1299. http://dx.doi.org/10.3390/jcm10061299.
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During the last years, accumulating evidence has suggested that the gut microbiota plays a key role in the pathogenesis of neurodevelopmental and neurodegenerative diseases via the gut–brain axis. Moreover, current research has helped to elucidate different communication pathways between the gut microbiota and neural tissues (e.g., the vagus nerve, tryptophan production, extrinsic enteric-associated neurons, and short chain fatty acids). On the other hand, altering the composition of gut microbiota promotes a state known as dysbiosis, where the balance between helpful and pathogenic bacteria is disrupted, usually stimulating the last ones. Herein, we summarize selected findings of the recent literature concerning the gut microbiome on the onset and progression of neurodevelopmental and degenerative disorders, and the strategies to modulate its composition in the search for therapeutical approaches, focusing mainly on animal models studies. Readers are advised that this is a young field, based on early studies, that is rapidly growing and being updated as the field advances.
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Breeze, Robert E., and Marjorie C. Wang. "An overview of central nervous system transplantation in human disease." Neurosurgical Focus 7, no. 3 (September 1999): E3. http://dx.doi.org/10.3171/foc.1999.7.3.4.
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Although its roots date back over a century, the field of neurotransplantation has been shaped mostly by advances over the past 30 years. Animal models of nigrostriatal disconnection in the 1970s allowed investigators to explore the feasibility of neural grafting. By the end of that decade, functional and behavioral effects had been demonstrated using fetal tissue grafts. In the 1980s, animal experimentation continued, as did clinical trials involving patients with idiopathic Parkinson's disease. Both autologous adrenal medullary tissue and fetal allografts were tested in the clinical setting, with the latter proving to yield superior results. Animal models of striatal cell loss provided the impetus for limited clinical trials in patients with Huntington's disease by the early 1990s, and work with both diseases continues today. Although much has been learned, neural grafting remains experimental. Broader applications are being explored even now, though, as transplant techniques are applied to animal models of dementia, spinal cord injury, cortical injury, and pain. Some very limited human trials have already begun in some of these areas. In this review some of the advances in the field are highlighted.
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Wrzosek, Marcin. "Electroencephalography as a diagnostic technique for canine neurological diseases." Journal of Veterinary Research 60, no. 2 (June 1, 2016): 181–87. http://dx.doi.org/10.1515/jvetres-2016-0027.
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Abstract Electroencephalography (EEG) is a non-invasive examination method for the assessment of functional central nervous system (CNS) disturbances. In human medicine it has a special importance as a diagnostic tool for epilepsy. Although many studies were done on the use of EEG for diagnostics of canine central nervous system disorders, the technique is still not applied routinely. The purpose of this paper was to review the use of the electroencephalography in canine neurological disorders of central nervous system diagnosis and assess the future perspectives of this technique in veterinary medicine.
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Chaumont, H., E. Roze, B. Tressières, F. Lazarini, and A. Lannuzel. "Central nervous system infections in a tropical area: influence of emerging and rare infections." European Journal of Neurology 27, no. 11 (July 27, 2020): 2242–49. http://dx.doi.org/10.1111/ene.14422.
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Csaba, György. "Hormonal imprinting in the central nervous system: causes and consequences." Orvosi Hetilap 154, no. 4 (January 2013): 128–35. http://dx.doi.org/10.1556/oh.2013.29533.
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The notion of the perinatal „hormonal imprinting” has been published at first in 1980 and since that time it spred expansively. The imprintig develops at the first encounter between the developing receptor and the target hormone – possibly by the alteration of the methylation pattern of DNA – and it is transmitted to the progeny generations of the cell. This is needed for the complete development of the receptor’s binding capacity. However, molecules similar to the target hormone (hormone-analogues, drugs, chemicals, environmental pollutants) can also bind to the developing receptor, causing faulty imprinting with life-long consequences. This can promote pathological conditions. Later it was cleared that in other critical periods such as puberty, imprinting also can be provoked, even in any age in differentiating cells. The central nervous system (brain) also can be mistakenly imprinted, which durably influences the dopaminergic, serotonergic and noradrenergic system and this can be manifested – in animal experiments – in alterations of the sexual and social behavior. In our modern age the faulty hormonal imprintig is inavoidable because of the mass of medicaments, chemicals, the presence of hormone-like materials (e.g. soya phytosteroids) in the food, and environmental pollutants. The author especially emphasizes the danger of oxytocin, as a perinatal imprinter, as it is used very broadly and can basically influence the emotional and social spheres and the appearance of certain diseases such as auitism, schizophrenia and parkinsonism. The danger of perinatal imprinters is growing, considering their effects on the human evolution. Orv. Hetil., 2013, 154, 128–135.
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Bain, Allison C., David I. Shreiber, and David F. Meaney. "Modeling of Microstructural Kinematics During Simple Elongation of Central Nervous System Tissue." Journal of Biomechanical Engineering 125, no. 6 (December 1, 2003): 798–804. http://dx.doi.org/10.1115/1.1632627.
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Damage to axons and glial cells in the central nervous system (CNS) white matter is a nearly universal feature of traumatic brain injury, yet it is not clear how the tissue mechanical deformations are transferred to the cellular components of the CNS. Defining how cellular deformations relate to the applied tissue deformation field can both highlight cellular populations at risk for mechanical injury, and define the fraction of cells in a specific population that will exhibit damage. In this investigation, microstructurally based models of CNS white matter were developed and tested against measured transformations of the CNS tissue microstructure under simple elongation. Results show that axons in the unstretched optic nerves were significantly wavy or undulated, where the measured axonal path length was greater than the end-to-end distance of the axon. The average undulation parameter—defined as the true axonal length divided by the end-to-end length—was 1.13. In stretched nerves, mean axonal undulations decreased with increasing applied stretch ratio (λ)—the mean undulation values decreased to 1.06 at λ=1.06, 1.04 at λ=1.12, and 1.02 at λ=1.25. A model describing the gradual coupling, or tethering, of the axons to the surrounding glial cells best fit the experimental data. These modeling efforts indicate the fraction of the axonal and glial populations experiencing deformation increases with applied elongation, consistent with the observation that both axonal and glial cell injury increases at higher levels of white matter injury. Ultimately, these results can be used in conjunction with computational simulations of traumatic brain injury to aid in establishing the relative risk of cellular structures in the CNS white matter to mechanical injury.
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Grommes, Christian, Alessandro Pastore, Igor Gavrilovic, Thomas Kaley, Craig Nolan, Antonio M. Omuro, Julia Wolfe, et al. "Single-Agent Ibrutinib in Recurrent/Refractory Central Nervous System Lymphoma." Blood 128, no. 22 (December 2, 2016): 783. http://dx.doi.org/10.1182/blood.v128.22.783.783.
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Abstract BACKGROUND: Primary Central Nervous System Lymphoma (PCNSL) is an aggressive primary brain tumor with median progression free survival (PFS) after upfront methotrexate-based chemotherapy of 2-3 years. Outcome and treatment options are poor for recurrent/refractory (r/r) disease. Response rates (ORR) range between 30-60% with a PFS of 2-5 months. Ibrutinib has shown promising clinical response in Mantel cell lymphoma, CLL, and Waldenström. This trial investigates Ibrutinib in patients with r/r PCNSL and SCNSL. METHODS: Eligible patients had r/r PCNSL or Secondary CNS Lymphoma (SCNSL), age≥18, ECOG≤2, normal end-organ function, and unrestricted number of CNS directed prior therapies. In patients with SCNSL disease, systemic disease needed to be absent. RESULTS: Twenty patients were enrolled (3 at 560 mg; 17 at 840 mg). Median age was 69 (range 21-85); 12 were women. Median ECOG was 1 (0: 2, 1: 12, 2: 6). 65% had PCNSL and 35% SCNSL; 70% had recurrent disease. Eleven had parenchymal disease, 3 isolated cerebrospinal fluid (CSF) involvement and 6 both. Five grade 4 adverse events were observed in 4 patients (lymphopenia (2), sepsis (1), neutropenia (2)). Ten patients developed grade 3 toxicities, including lymphopenia in 3 patients, thrombocytopenia in 2, hyperglycemia in 2, lung infection in 2, neutropenia in 1, urinary tract infection in 1, colitis in 1, and fungal encephalitis in 1. The most common toxicities were hyperglycemia, anemia, and thrombocytopenia. After a median follow-up of 193 days, 19/20 patients were evaluated for response: 8 CR, 7 PR, 1 SD and 3 PD; 75% (15/20) ORR. The median PFS is 7.29 months (95% CI: 3.80-15.43 months (longest: 15.3 months)). The mean Ibrutinib concentration in the CSF 2h post administration at day 1 and 29 is 1.75 ng/mL (3.97 nM) and 2.51 ng/mL (5.6 nM) which is above the IC50 (1nM) required in vitro to reduce growth of lymphoma cells.An additional treatment arm has been added to the trial which will evaluate adverse events of the combination of ibrutinib and high-dose methotrexate chemotherapy. Enrollment into the combination arm is ongoing and updates will be presented at the meeting. CONCLUSION: Patients with CNS lymphoma tolerate Ibrutinib with manageable adverse events. Drug concentrations in CSF are higher at steady state (day 29) and meaningful CSF concentrations are reached. Clinical response was seen in 75% of CNS lymphoma patients. A combination arm will assess the adverse events of ibrutinib in combination with high-dose methotrexate chemotherapy. Disclosures No relevant conflicts of interest to declare.
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Magee, C. A., M. Cahir, D. W. Halton, C. F. Johnston, and C. Shaw. "Cytochemical observations on the nervous system of adult Corrigia vitta." Journal of Helminthology 67, no. 3 (September 1993): 189–99. http://dx.doi.org/10.1017/s0022149x00013122.
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AbstractAdult Corrigia vitta (Trematoda: Dicrocoelidea) inhabit the pancreatic duct of the fieldmouse, Apodemus sylvaticus, where, in numbers, they may occlude the duct lumen and prevent the flow of pancreatic secretions. Enzyme histochemical and immunocytochemical techniques, in conjunction with confocal scanning laser microscopy, have been used to examine the localization and distribution of cholinergic. serotoninergic (5-HT, serotonin) and peptidergic components of the nervous system of the adult worm. All three classes of neuronal mediator showed a common pattern of staining, occurring throughout the central and peripheral nervous systems. Of the four peptide immunoreactivities (IR) demonstrated (pancreatic polypeptide (PP), peptide YY (PYY), substance P (SP), FMRFamide), PP-IR was the most predominant, occurring not only within the central ganglia and longitudinal nerve cords, but also in subtegumental plexuses and in fibres associated with the egg-forming apparatus. PYY and FMRFamide IRs were evident throughout the central and peripheral nervous systems; FMRFamide immunostaining, in particular, highlighted innervation of the ootype and immunoreactive cell bodies around the Mehlis' gland. Both SP- and 5-HT-IRs were restricted to the cerebral ganglia, ventral nerve cords and associated cell bodies. The distribution pattems of these peptides and 5-HT within the nervous system of C. vitta suggest they are likely to function as neuronal mediators. PP, PYY and FMRFamide may also serve in regulating egg production.
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Li, Xun, Shifeng Chu, Yinjiao Liu, and Naihong Chen. "Neuroprotective Effects of Anthraquinones from Rhubarb in Central Nervous System Diseases." Evidence-Based Complementary and Alternative Medicine 2019 (May 16, 2019): 1–12. http://dx.doi.org/10.1155/2019/3790728.
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Rhubarb is a well-known traditional Chinese medicine; it has been used in China for thousands of years. Rhubarb anthraquinones are the major medicinal ingredients derived from rhubarb including emodin, aloe-emodin, chrysophanol, rhein, physcion, and danthron. These different anthraquinone derivatives alone or in combination play a therapeutic role in central nervous system diseases (CNSD), such as cerebral ischemic stroke, intracerebral hemorrhage, traumatic brain injury, brain tumor, Alzheimer’s disease, depression, and others. We review the experimental studies on these six anthraquinones in the treatment of CNSD by consulting literature published in the last 20 years in PubMed and then give a future perspective on it. In the end of this paper some deficiencies related to these studies also have been pointed out.
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Trojanowski, J. Q. "Neurofilament proteins and human nervous system tumors." Journal of Histochemistry & Cytochemistry 35, no. 9 (September 1987): 999–1003. http://dx.doi.org/10.1177/35.9.3611738.
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Neoplasms that arise in the peripheral (e.g., carotid body tumors, neuroblastomas, pheochromocytomas) or central (gangliocytomas, medulloblastomas) nervous system express a number of neuron-specific gene products. Presumably, these tumors are derived from precursor cells that are or have the potential to develop into neurons or neuron-like cells. This report provides a critical examination of the hypothesis that cytoskeletal proteins of normal neurons, in particular the neuron-specific class of intermediate filaments (neurofilaments), are present but are abnormal in neoplasms derived from neurons or neuron-like cells. The implications of these findings for understanding tumor promotion and progression, and for development of molecular probes for the diagnostic assessment of these neoplasms, are discussed.
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Martín-Durán, José M., Gabriella H. Wolff, Nicholas J. Strausfeld, and Andreas Hejnol. "The larval nervous system of the penis worm Priapulus caudatus (Ecdysozoa)." Philosophical Transactions of the Royal Society B: Biological Sciences 371, no. 1685 (January 5, 2016): 20150050. http://dx.doi.org/10.1098/rstb.2015.0050.
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The origin and extreme diversification of the animal nervous system is a central question in biology. While most of the attention has traditionally been paid to those lineages with highly elaborated nervous systems (e.g. arthropods, vertebrates, annelids), only the study of the vast animal diversity can deliver a comprehensive view of the evolutionary history of this organ system. In this regard, the phylogenetic position and apparently conservative molecular, morphological and embryological features of priapulid worms (Priapulida) place this animal lineage as a key to understanding the evolution of the Ecdysozoa (i.e. arthropods and nematodes). In this study, we characterize the nervous system of the hatching larva and first lorica larva of the priapulid worm Priapulus caudatus by immunolabelling against acetylated and tyrosinated tubulin, pCaMKII, serotonin and FMRFamide. Our results show that a circumoral brain and an unpaired ventral nerve with a caudal ganglion characterize the central nervous system of hatching embryos. After the first moult, the larva attains some adult features: a neck ganglion, an introvert plexus, and conspicuous secondary longitudinal neurites. Our study delivers a neuroanatomical framework for future embryological studies in priapulid worms, and helps illuminate the course of nervous system evolution in the Ecdysozoa.
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Musumeci, O., S. Marino, F. Granata, R. Morabito, L. Bonanno, T. Brizzi, V. Lo Buono, F. Corallo, M. Longo, and A. Toscano. "Central nervous system involvement in late‐onset Pompe disease: clues from neuroimaging and neuropsychological analysis." European Journal of Neurology 26, no. 3 (November 15, 2018): 442. http://dx.doi.org/10.1111/ene.13835.
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Zakaria, Mohamed Naguib, Hany M. El-Bassossy, and Waleed Barakat. "Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats." Advances in Pharmacological Sciences 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/346259.
Full textAbstract:
Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE) and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular andcentral nervous system(CNS) complications in STZ-induced (50 mg/kg, IP) diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze), neuronal degeneration (Fluoro-Jade staining), AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde). These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications.
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Gironacci, Mariela M., Nadia A. Longo Carbajosa, Jorge Goldstein, and Bruno D. Cerrato. "Neuromodulatory role of angiotensin-(1–7) in the central nervous system." Clinical Science 125, no. 2 (March 26, 2013): 57–65. http://dx.doi.org/10.1042/cs20120652.
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Ang-(1–7) [angiotensin-(1–7)] constitutes an important functional end-product of the RAS (renin–angiotensin system) endogenously formed from AngI (angiotensin I) or AngII (angiotensin II) through the catalytic activity of ACE2 (angiotensin-converting enzyme 2), prolyl carboxypeptidase, neutral endopeptidase or other endopeptidases. Ang-(1–7) lacks the pressor, dipsogenic or stimulatory effect on aldosterone release characteristic of AngII. In contrast, it produces vasodilation, natriuresis and diuresis, and inhibits angiogenesis and cell growth. At the central level, Ang-(1–7) acts at sites involved in the control of cardiovascular function, thus contributing to blood pressure regulation. This action may result from its inhibitory neuromodulatory action on NE [noradrenaline (norepinephrine)] levels at the synaptic cleft, i.e. Ang-(1–7) reduces NE release and synthesis, whereas it causes an increase in NE transporter expression, contributing in this way to central NE neuromodulation. Thus, by selective neurotransmitter release, Ang-(1–7) may contribute to the overall central cardiovascular effects. In the present review, we summarize the central effects of Ang-(1–7) and the mechanism by which the peptide modulates NE levels in the synaptic cleft. We also provide new evidences of its cerebroprotective role.
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Chen, Yu-Shuan, Horng-Jyh Harn, and Tzyy-Wen Chiou. "The Role of Biomaterials in Implantation for Central Nervous System Injury." Cell Transplantation 27, no. 3 (March 2018): 407–22. http://dx.doi.org/10.1177/0963689717732991.
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Permanent deficits that occur in memory, sensation, and cognition can result from central nervous system (CNS) trauma that causes dysfunction and/or unregulated CNS regeneration. Some therapeutic approaches are preferentially applied to the human body. Therefore, cell transplantation, one of the therapeutic strategies, may be used to benefit people. However, poor cell viability and low efficacy are the limitations to cell transplantation strategies. Biomaterials have been widely used in several fields (e.g., triggering cell differentiation, guiding cell migration, improving wound healing, and increasing tissue regeneration) by modulating their characteristics in chemistry, topography, and softness/stiffness for highly flexible application. We reviewed implanted biomaterials to investigate the roles and influences of physical/chemical properties on cell behaviors and applications. With their unique molecular features, biomaterials are delivered in several methods and mixed with transplanted cells, which assists in increasing postimplanted biological substance efficiency on cell survival, host responses, and functional recovery of animal models. Moreover, tracking the routes of these transplanted cells using biomaterials as labeling agents is crucial for addressing their location, distribution, activity, and viability. Here, we provide comprehensive comments and up-to-date research of the application of biomaterials.
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Wąsik, Norbert, Roman Jankowski, Bartosz Sokół, and Hinna Shahid. "High mobility group box 1 protein in the central nervous system." Journal of Medical Science 83, no. 4 (December 31, 2014): 336–41. http://dx.doi.org/10.20883/medical.e89.
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High-mobility group box 1 protein (HMGB1) is a multifunctional protein originally identified as a nuclear transcription modifier. Two pathways are leading to HMGB1 release to the extracellular space i.e. active secretion triggered by noxious stimulation and passive leakage due to necrotic membrane damage. Binding with receptors for advanced glycation end products (RAGE) as well as Toll-like receptor 2 (TLR2) and TLR4 leads to nuclear factor ?B (NF-?B) activation and proinflammatory reaction in target cells. Secretion of cytokines, upregulation of adhesion molecules and chemoattraction are triggered by the extracellular HMGB1. Such ubiquitous and numerous protein plays a role in pathogenesis of many common diseases like sepsis, rheumatoid arthritis and pneumonia. Central nervous system (CNS) disorders are also mediated by HMGB1. Multiple studies highlight pivotal role of HMGB1 in acute pathologies of CNS like cerebral ischemia, aneurysmal subarachnoid hemorrhage as well as chronic degenerative disorders such as Alzheimer’s disease and multiple sclerosis. Wide range of HMGB1 antagonists are currently investigated as novel therapeutic agents in sepsis, colitis and stroke. This review article provides basic information about HMGB1 protein and its role in the pathogenesis of CNS diseases.
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Jensen, Garrett L., Bouthaina S. Dabaja, Chelsea C. Pinnix, Jillian R. Gunther, Auris Huen, Madeleine Duvic, Yasuhiro Oki, Michelle Fanale, Chitra Hosing, and Sarah A. Milgrom. "Radiotherapy in Patients with Mycosis Fungoides and Central Nervous System Involvement." Case Reports in Oncology 11, no. 3 (November 12, 2018): 721–28. http://dx.doi.org/10.1159/000494081.
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Background: Involvement of the central nervous system (CNS) by mycosis fungoides (MF) is rare; however, it portends a poor prognosis. While aggressive multimodality therapy may improve outcomes, the role of radiation therapy (RT) is not well defined. Objectives: We sought to explore the efficacy of RT in the management of CNS involvement by MF. Method: We retrospectively identified five patients with MF and CNS involvement who received cranial or craniospinal RT at a single institution. Patient characteristics, disease features, radiographic findings, treatments delivered, and outcome data were extracted from the electronic medical record. Results: All 5 patients had neurologic deficits at RT initiation, and 4 experienced at least a partial improvement. Of 4 patients evaluated by MRI after RT completion, 3 had complete resolution of CNS disease within the irradiated field. At the time of last follow-up, all patients had died of MF. The median time to death was 7.4 months (range 1.0–21 months) from their diagnosis with CNS involvement and 1.2 months (range 0.4–7.1 months) from the end of RT treatment. Conclusions: We observed high rates of radiographic response and palliation of neurological symptoms. Nonetheless, all patients succumbed to their disease shortly after treatment, confirming the poor prognosis of this condition. Our findings suggest that RT may play a valuable palliative role for these patients.
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Cameron, Michelle H. "The WalkAide® Functional Electrical Stimulation System - A Novel Therapeutic Approach For Foot Drop in Central Nervous System Disorders." European Neurological Review 5, no. 2 (2010): 18. http://dx.doi.org/10.17925/enr.2010.05.02.18.
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Foot drop is the inability to voluntarily dorsiflex the ankle during the swing phase of gait. Foot drop decreases gait quality, limits mobility, increases fall risk, and greatly increases energy expenditure during walking. Traditionally, foot drop is treated with passive dorsiflexion support by an ankle foot orthosis (AFO) but today, functional electrical stimulation (FES) devices are available to promote comfortable, effective active dorsiflexion during gait for patients with central nervous system (CNS) causes of foot drop. The WalkAide® FES System’s unique control system, with tilt sensors to trigger electrical stimulation during the swing phase, can help normalise gait and thus optimise safety, cosmesis and energy efficiency in people with stroke, multiple sclerosis, cerebral palsy and a wide range of other CNS disorders.