scholarly journals Gaseous neurotransmitter nitric oxide: Its role in experimental models of epilepsy

2012 ◽  
Vol 64 (3) ◽  
pp. 1207-1216 ◽  
Author(s):  
D. Hrncic ◽  
Aleksandra Rasic-Markovic ◽  
Jelica Bjekic-Macut ◽  
Veselinka Susic ◽  
D. Mladenovic ◽  
...  

Epilepsy is one of the leading neurological disorders and affects 1-2% of the world?s population. Generally, it is a result of an imbalance between excitatory and inhibitory phenomena in the central nervous system (CNS), but the mechanisms of its initiation and propagation still require further investigations. Experimental models represent one of the most powerful tools to better understand the mechanisms of epileptogenesis. Nitric oxide (NO) is gaseous molecule with pleiotropic physiological and pathological effects in almost all organ systems and intriguing biological relevance, especially in the CNS where it acts as a gaseous neurotransmitter. The role of NO in the generation of epilepsy is highly contradictory, since there is evidence of its anticonvulsive, as well as proconvulsive properties. Therefore, we will discuss in this review the involvement of NO-mediated signaling pathways in the mechanisms of epileptogenesis, taking into account the findings revealed in experimental studies on animal models of epilepsy.

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1449
Author(s):  
Jae-Won Lee ◽  
Wanjoo Chun ◽  
Hee Jae Lee ◽  
Seong-Man Kim ◽  
Jae-Hong Min ◽  
...  

Microglia play an important role in the maintenance and neuroprotection of the central nervous system (CNS) by removing pathogens, damaged neurons, and plaques. Recent observations emphasize that the promotion and development of neurodegenerative diseases (NDs) are closely related to microglial activation. In this review, we summarize the contribution of microglial activation and its associated mechanisms in NDs, such as epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), based on recent observations. This review also briefly introduces experimental animal models of epilepsy, AD, PD, and HD. Thus, this review provides a better understanding of microglial functions in the development of NDs, suggesting that microglial targeting could be an effective therapeutic strategy for these diseases.


2021 ◽  
Author(s):  
Y.I. Belova ◽  
O.V. Yakovleva

Nitrogen monoxide is a gas transmitter that is an important intermediary in many organ systems, especially in the central nervous system. Nitrogen monoxide is involved in the relaxation of smooth vascular muscles, activation of neurons and responsible for the cytotoxicity of macrophages. The study of change nitrogen oxide metabolite concentration helps to determine its effects on human and animal organs. The study was carried out on laboratory animals of different ages. We used a spectrophotometric method to determine the level of metabolites based on the reaction of nitrites to the Griss reagent. We noted that the maximum level of metabolites NO was observed in newborn animals at the age of 4 days. In addition, metabolite concentrations decreased gradually by 14-15 days of life, reaching a minimum of 30 days Key words: nitrogen monoxide, rats, age, metabolites of nitrogen monoxide, spectrophotometry.


2004 ◽  
Vol 57 (7-8) ◽  
pp. 359-362 ◽  
Author(s):  
Olivera Stanojlovic ◽  
Dragana Zivanovic

Introduction An epileptic seizure is a clinical event and epilepsy is rather a group of symptoms than a disease. The main features all epilepsies have in common include: spontaneous occurrence, repetitiveness, and ictal correlation within the EEG. Epilepsies are manifested with distinct EEG changes, requiring exact clinical definition and consequential treatment. Current data show that 1% of the world's population (approximately 50 million people) suffers from epilepsy, with 25% of patients being refractory to therapy and requiring search for new substances in order to decrease EEG and behavioral manifestations of epilepsies. Material and methods In regard to discovery and testing of anticonvulsant substances the best results were achieved by implementation of experi- mental models. Animal models of epilepsy are useful in acquiring basic knowledge regarding pathogenesis, neurotransmitters (glutamate), receptors (NMDA/AMPA/kainate), propagation of epileptic seizures and preclinical assessment of antiepileptics (competitive and non-competitive NMDA antagonists). Results and conclusions In our lab, we have developed a pharmacologic model of a (metaphit, NMDA and remacemide-cilastatin) generalized, reflex, and audiogenic epilepsy. The model is suitable for testing various anticonvulsant substances (e.g. APH, APV, CPP, Mk-801) and potential antiepileptics (e.g. DSIP, its tetra- and octaanalogues).


2014 ◽  
Vol 114 (4) ◽  
pp. 730-737 ◽  
Author(s):  
David J. Polhemus ◽  
David J. Lefer

Long recognized as a malodorous and highly toxic gas, recent experimental studies have revealed that hydrogen sulfide (H 2 S) is produced enzymatically in all mammalian species including man and exerts several critical actions to promote cardiovascular homeostasis and health. During the past 15 years, scientists have determined that H 2 S is produced by 3 endogenous enzymes and exerts powerful effects on endothelial cells, smooth muscle cells, inflammatory cells, mitochondria, endoplasmic reticulum, and nuclear transcription factors. These effects have been reported in multiple organ systems, and the majority of data clearly indicate that H 2 S produced by the endogenous enzymes exerts cytoprotective actions. Recent preclinical studies investigating cardiovascular diseases have demonstrated that the administration of physiological or pharmacological levels of H 2 S attenuates myocardial injury, protects blood vessels, limits inflammation, and regulates blood pressure. H 2 S has emerged as a critical cardiovascular signaling molecule similar to nitric oxide and carbon monoxide with a profound effect on the heart and circulation. Our improved understanding of how H 2 S elicits protective actions, coupled with the rapid development of novel H 2 S-releasing agents, has resulted in heightened enthusiasm for the clinical translation of this ephemeral gaseous molecule. This review will examine our current state of knowledge about the actions of H 2 S within the cardiovascular system with an emphasis on the therapeutic potential and molecular cross talk between H 2 S, nitric oxide, and carbon monoxide.


Author(s):  
Б.И. Гельцер ◽  
Э.В. Слабенко ◽  
Ю.В. Заяц ◽  
В.Н. Котельников

Одним из основных требований к разработке экспериментальных моделей цереброваскулярных заболеваний является их максимальная приближенность к реальной клинической практике. В работе систематизированы данные по основным методам моделирования острой ишемии головного мозга (ОИГМ), представлена их классификация, анализируются данные о преимуществах и недостатках той или иной модели. Обсуждаются результаты экспериментальных исследований по изучению патогенеза ОИГМ с использованием различных моделей (полной и неполной глобальной, локальной и мультифокальной ишемии) и способов их реализации (перевязка артерий, клипирование, коагуляция, эмболизация и др.). Особое внимание уделяется «стабильности» последствий острого нарушения мозгового кровообращения: необратимых ишемических повреждений головного мозга или обратимых с реперфузией заданной продолжительности. Отмечается, что важное значение в этих исследованиях должно принадлежать современным методам прижизненной визуализации очагов острого ишемического повреждения, что позволяет оценивать динамику патологического процесса. Предлагаемый метод отвечает требованиям гуманного обращения с животными. Подчеркивается, что выбор релевантной модели ОИГМ определяется задачами предстоящего исследования и технологическими ресурсами научной лаборатории. Development of experimental models for acute forms of cerebrovascular diseases is essential for implementation of methods for their prevention and treatment. One of the principal requirements to such models is their maximum approximation to actual clinical practice. This review systematized major models of acute cerebral ischemia (ACI), their classification, and presented information about their advantages and shortcomings. Also, the review presented results of experimental studies on pathophysiological mechanisms of different types of modeled ACI (complete and incomplete global, local, and multifocal ischemia) and methods for creating these models (arterial ligation, clipping, coagulation, embolization, etc.). Particular attention was paid to “stability” of the consequences of acutely impaired cerebral circulation - an irreversible ischemic brain injury or a reversible injury with reperfusion of a given duration. The authors emphasized that in such studies, a special significance should be given to intravital imaging of acute ischemic damage foci using modern methods, which allow assessing the dynamics of the pathological process and meet the requirements to humane treatment of animals. The choice of a relevant ACI model is determined by objectives of the planned study and the technological resources available at the research laboratory.


Author(s):  
Christian Muschitz ◽  
Anita Trummert ◽  
Theresa Berent ◽  
Norbert Laimer ◽  
Lukas Knoblich ◽  
...  

SummarySevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), produces protean manifestations and causes indiscriminate havoc in multiple organ systems. This rapid and vast production of proinflammatory cytokines contributes to a condition termed cytokine storm. A 35-year-old, otherwise healthy, employed, male patient was tested positive for COVID-19. He was admitted to the hospital on disease day 10 due to retarded verbal reactions and progressive delirium. On account of these conditions and the need for noninvasive/invasive ventilation, a combination treatment with baricitinib and remdesivir in conjunction with standard of care was initiated. The cytokine storm was rapidly blocked, leading to a vast pulmonary recovery with retarded recovery of the central nervous system. We conclude that the rapid blockade of the COVID-19-induced cytokine storm should be considered of avail as a principle of careful decision-making for effective recovery.


Author(s):  
Natalia Nowak ◽  
Masayuki Yamanouchi ◽  
Eiichiro Satake

AbstractExtracellular vesicle (EV)-based therapy was hypothesized as a promising regenerative approach which has led to intensive research of EVs in various pathologies. In this study, we performed a comprehensive systematic review of the current experimental evidence regarding the protective properties of EVs in chronic kidney disease (CKD). We evaluated the EV-based experiments, EV characteristics, and effector molecules with their involvement in CKD pathways. Including all animal records with available creatinine or urea data, we performed a stratified univariable meta-analysis to assess the determinants of EV-based therapy effectiveness. We identified 35 interventional studies that assessed nephroprotective role of EVs and catalogued them according to their involvement in CKD mechanism. Systematic assessment of these studies suggested that EVs had consistently improved glomerulosclerosis, interstitial fibrosis, and cell damage, among different CKD models. Moreover, EV-based therapy reduced the progression of renal decline in CKD. The stratified analyses showed that the disease model, administered dose, and time of therapeutic intervention were potential predictors of therapeutic efficacy. Together, EV therapy is a promising approach for CKD progression in experimental studies. Further standardisation of EV-methods, continuous improvement of the study quality, and better understanding of the determinants of EV effectiveness will facilitate preclinical research, and may help development of clinical trials in people with CKD. Graphical Abstract


1996 ◽  
Vol 54 (2) ◽  
pp. 331-334 ◽  
Author(s):  
L. A. V Peireira ◽  
M. A. Cruz-Höfling ◽  
M. S. J. Dertkigil ◽  
D. L. Graça

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.


2007 ◽  
Vol 292 (3) ◽  
pp. E654-E667 ◽  
Author(s):  
Dake Qi ◽  
Brian Rodrigues

Insulin resistance is viewed as an insufficiency in insulin action, with glucocorticoids being recognized to play a key role in its pathogenesis. With insulin resistance, metabolism in multiple organ systems such as skeletal muscle, liver, and adipose tissue is altered. These metabolic alterations are widely believed to be important factors in the morbidity and mortality of cardiovascular disease. More importantly, clinical and experimental studies have established that metabolic abnormalities in the heart per se also play a crucial role in the development of heart failure. Following glucocorticoids, glucose utilization is compromised in the heart. This attenuated glucose metabolism is associated with altered fatty acid supply, composition, and utilization. In the heart, elevated fatty acid use has been implicated in a number of metabolic, morphological, and mechanical changes and, more recently, in “lipotoxicity”. In the present article, we review the action of glucocorticoids, their role in insulin resistance, and their influence in modulating peripheral and cardiac metabolism and heart disease.


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