scholarly journals Neuroprotective and cerebrovascular effects of endogenous N-Arachidonoyl-GABA and its putative Cox-2 metabolite – GABA conjugate with Prostaglandin E2

2021 ◽  
Vol 7 (3) ◽  
pp. 49-61
Author(s):  
Narine R. Mirzoyan ◽  
Nelly G. Khostikyan ◽  
Vahe S. Meliksetyan ◽  
Arpine A. Hakobyan ◽  
Tamara S. Gan’shina ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Prostaglandin E2 ◽  
Brain Tissue ◽  
Brain Ischemia ◽  
Cerebral Circulation ◽  
Transient Ischemia ◽  
Cox 2 ◽  
The Brain ◽  
Rat Brain Tissue

Introduction: The aim of the study was to compare the neuroprotective and cerebrovascular effects of bioactive, endogenous lipid – N-arachidonoyl-GABA (AA-GABA) and GABA conjugate with prostaglandin E2 (PGE2-GABA) by evaluation of a morphological state of rat brain tissue and lipofuscin levels under the condition of permanent focal brain ischemia, as well as cerebral circulation under the condition of global transient ischemia. Materials and methods: The study has been implemented using the models of the left middle cerebral artery occlusion (MCAO) and global transient ischemia of the brain. A morphological examination of the brain tissue, a registration of local blood flow by laser flowmeter, and quantitative measurement of lipofuscin by fluorescence spectroscopy were used. Results and discussion: AA-GABA and the putative COX-2 metabolite PGE2-GABA showed significant neuroprotective and cerebrovascular effects in rat models of global and focal cerebral ischemia. In the MCAO model, AA-GABA and PGE2-GABA at a dose of 2 mg/kg/day administered i.p. for 6 or 12 days led to: 1) significant restoration of neurons and glial cells with intracellular regeneration of cytoplasmic and nuclear structures, 2) decrease in brain tissue edema; 3) attenuated thrombosis and stasis, and 4) absence of large necrotic foci in rat brain tissue. AA-GABA and PGE2-GABA at the same dose prevented excessive accumulation of lipofuscin in both brain hemispheres in rats with MCAO. All the studied compounds increase cerebral blood circulation in rats subjected to global transient ischemia. However, the cerebrovascular effect of PGE2-GABA was superior to the activity of AA-GABA and all other tested compounds. AA-GABA and PGE2-GABA, unlike PGE2 and nimodipine, increase the cerebral blood flow in rats with global transient brain ischemia and have no influence on the intact animals. Apparently, the GABAergic vascular system of the brain is involved in the mechanisms of the neuroprotective action of AA-GABA and PGE2-GABA. Conclusion: For the first time, we demonstrated the ability of AA-GABA and its putative metabolite COX-2 PGE2-GABA to improve cerebral circulation, attenuate structural damage and lipofuscin accumulation during cerebral ischemia. The natural origin of AA-GABA, which possesses neuroprotective and cerebrovascular activity, as well as anti-aggregatory activity, allows considering AA-GABA as one of the endogenous protective factors in ischemic brain lesions. Graphical abstract:

scholarly journals Cerebrovascular and Neuroprotective Effects of Adamantane Derivative

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ruben S. Mirzoyan ◽  
Tamara S. Gan’shina ◽  
Denis V. Maslennikov ◽  
Georgy I. Kovalev ◽  
Ivan A. Zimin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Nmda Receptors ◽  
Middle Cerebral Artery ◽  
Brain Tissue ◽  
Cerebral Artery ◽  
Brain Ischemia ◽  
Adamantane Derivative ◽  
Neuroprotective Activity ◽  
Neuroprotective Effects ◽  
The Brain

Objectives. The influence of 5-hydroxyadamantane-2-on was studied on the rats’ brain blood flow and on morphological state of brain tissue under the condition of brain ischemia. The interaction of the substance with NMDA receptors was also studied.Methods. Study has been implemented using the methods of local blood flow registration by laser flowmeter, [3H]-MK-801binding, and morphological examination of the brain tissue. We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, and hypergravity ischemia of the brain.Results. Unlike memantine, antagonist of glutamatergic receptors, the 5-hydroxyadamantane-2-on does not block NMDA receptors but enhances the cerebral blood flow of rats with brain ischemia. This effect is eliminated by bicuculline. Under conditions of permanent occlusion of middle cerebral artery, 5-hydroxyadamantane-2-on has recovered compensatory regeneration in neural cells, axons, and glial cells, and the number of microcirculatory vessels was increased. 5-Hydroxyadamantane-2-on was increasing the survival rate of animals with hypergravity ischemia.Conclusions. 5-Hydroxyadamantane-2-on, an adamantane derivative, which is not NMDA receptors antagonist, demonstrates significant cerebrovascular and neuroprotective activity in conditions of brain ischemia. Presumably, the GABA-ergic system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-hydroxyadamantane-2-on.

scholarly journals Chronic Brain Ischemia: From Risk Factors to Cerebrovascular Complications

2021 ◽  
Vol 7 (6) ◽  
Author(s):  
F. Yusupov ◽  
Sh. Nurmatov ◽  
N. Abdykalykova ◽  
A. Yuldashev ◽  
M. Abdykadyrov
Keyword(s):  
Risk Factors ◽  
Cerebral Ischemia ◽  
Arterial Hypertension ◽  
Brain Tissue ◽  
Brain Ischemia ◽  
Chronic Cerebral Ischemia ◽  
Cerebrovascular Complications ◽  
Cerebral Blood Supply ◽  
Chronic Brain Ischemia ◽  
The Brain

Chronic cerebral ischemia is a polyetiological, chronic progressive dysfunction of the brain caused by diffuse and / or small focal damage to the brain tissue in conditions of prolonged insufficiency of cerebral blood supply. The review reflects the current understanding of chronic cerebral ischemia. The main pathogenetic mechanisms of the onset of chronic cerebral ischemia in patients with arterial hypertension, atherosclerosis and smoking are outlined.

Neuroprotection and Angiogenesis: Dual Role of Erythropoietin in Brain Ischemia

Physiology ◽  
2000 ◽  
Vol 15 (5) ◽  
pp. 225-229 ◽  
Author(s):  
Hugo H. Marti ◽  
Myriam Bernaudin ◽  
Edwige Petit ◽  
Christian Bauer
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Protective Effect ◽  
Brain Tissue ◽  
Brain Ischemia ◽  
Vessel Growth ◽  
The Brain ◽  
Indirect Protection ◽  
Brain Vessel

Erythropoietin, originally defined as an erythroid growth factor, is upregulated in the brain under conditions of hypoxia. So far, two functions have been identified for this locally produced cytokine: a direct protective effect on neuronal cells during cerebral ischemia and an indirect protection of brain tissue that could be provided by promoting brain vessel growth.

Liquid Chromatography Analysis of Clozapine in Rat Brain Tissue, Using its Molecularly Imprinted Polymer after Administration of Toxic Dose of Drug and Lipid Emulsion Therapy

2019 ◽  
Vol 15 (3) ◽  
pp. 251-257
Author(s):  
Bahareh Sadat Yousefsani ◽  
Seyed Ahmad Mohajeri ◽  
Mohammad Moshiri ◽  
Hossein Hosseinzadeh
Keyword(s):  
Rat Brain ◽  
Brain Tissue ◽  
Molecularly Imprinted Polymer ◽  
Lipid Emulsion ◽  
Limit Of Detection ◽  
Imprinted Polymer ◽  
Toxic Dose ◽  
Molecularly Imprinted ◽  
The Brain ◽  
Rat Brain Tissue

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

scholarly journals Expression of NMDA receptor and microRNA-219 in rats submitted to cerebral ischemia associated with alcoholism

2017 ◽  
Vol 75 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Cristiane Iozzi Silva ◽  
Paulo Cézar Novais ◽  
Andressa Romualdo Rodrigues ◽  
Camila A.M. Carvalho ◽  
Benedicto Oscar Colli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Wistar Rats ◽  
Molecular Mechanisms ◽  
Inverse Correlation ◽  
Control Group ◽  
The Brain ◽  
Lower Expression ◽  
Control Sham

ABSTRACT Alcohol consumption aggravates injuries caused by ischemia. Many molecular mechanisms are involved in the pathophysiology of cerebral ischemia, including neurotransmitter expression, which is regulated by microRNAs. Objective: To evaluate the microRNA-219 and NMDA expression in brain tissue and blood of animals subjected to cerebral ischemia associated with alcoholism. Methods: Fifty Wistar rats were divided into groups: control, sham, ischemic, alcoholic, and ischemic plus alcoholic. The expression of microRNA-219 and NMDA were analyzed by real-time PCR. Results: When compared to the control group, the microRNA-219 in brain tissue was less expressed in the ischemic, alcoholic, and ischemic plus alcoholic groups. In the blood, this microRNA had lower expression in alcoholic and ischemic plus alcoholic groups. In the brain tissue the NMDA gene expression was greater in the ischemic, alcoholic, and ischemic plus alcoholic groups. Conclusion: A possible modulation of NMDA by microRNA-219 was observed with an inverse correlation between them.

scholarly journals Accessing neuroinflammation sites: Monocyte/neutrophil-mediated drug delivery for cerebral ischemia

2019 ◽  
Vol 5 (7) ◽  
pp. eaau8301 ◽  
Author(s):  
Jia Hou ◽  
Xu Yang ◽  
Shiyi Li ◽  
Zhekang Cheng ◽  
Yuhua Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Flow ◽  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Target Cells ◽  
Ischemic Brain ◽  
Therapeutic Molecules ◽  
Cerebral Parenchyma ◽  
Cell Carriers ◽  
The Brain

Cerebral ischemia (CI) results from inadequate blood flow to the brain. The difficulty of delivering therapeutic molecules to lesions resulting from CI hinders the effective treatment of this disease. The inflammatory response following CI offers a unique opportunity for drug delivery to the ischemic brain and targeted cells because of the recruitment of leukocytes to the stroke core and penumbra. In the present study, neutrophils and monocytes were explored as cell carriers after selectively carrying cRGD liposomes, which effectively transmigrated the blood-brain barrier, infiltrated the cerebral parenchyma, and delivered therapeutic molecules to the injured sites and target cells. Our results showed the successful comigration of liposomes with neutrophils/monocytes and that both monocytes and neutrophils were important for successful delivery. Enhanced protection against ischemic injury was achieved in the CI/reperfusion model. The strategy presented here shows potential in the treatment of CI and other diseases related to inflammation.

scholarly journals Fangchinoline ameliorates the expressions of angiogenic molecule in cerebral ischemia induced neuronal degeneration in neonatal rats

2018 ◽  
Vol 9 (1) ◽  
pp. 117-122
Author(s):  
Han Daicheng ◽  
Xia Shiwen ◽  
Zhu Huaping ◽  
Liu Yong ◽  
Zhou Qianqian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Neuronal Degeneration ◽  
Neuronal Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neonatal Rats ◽  
Markers Of Oxidative Stress ◽  
The Brain

AbstractBackgroundPresent investigation evaluates the beneficial effect of fangchinoline on cerebral ischemia induced neuronal degeneration in neonatal rats and also postulates the possible mechanism of its action.MethodologyCerebral ischemia was produced by the ligation of right common carotid artery in neonatal rats on postnatal day 5 (P5) and further pups were treated with fangchinoline 3, 10 and 30 mg/kg, i.p. for the period of 3 days. Effect of fangchinoline was estimated by determining the brain injury and enzyme linked immunosorbent assay (ELISA) method was used for the estimation of pro-inflammatory mediators and markers of oxidative stress in the cerebral tissues of neonatal rats. Moreover western blot assay and histopathology study was also performed on the brain tissue.ResultsResult of this investigation reveals that the percentage of brain injury significantly reduces and enhancement of myelin basic protein in the cerebral tissues of fangchinoline than ischemic group. Treatment with fangchinoline attenuates the altered level of proinflammatory mediators and markers of oxidative stress in the cerebral tissue of cerebral ischemia induced neuronal injury neonatal rats. Moreover expressions of inducible nitric oxide synthtase (iNOS), vascular endothelial growth factor (VEGF), p53 and nuclear receptor factor-2 (Nrf2) in the brain tissue attenuated by fangchinoline treated group.ConclusionIn conclusion, fangchinoline ameliorates the cerebral ischemia induced neuronal injury in neonatal rats by enhancing angiogenesis molecules.

Cooling Penetration Surrounding an Intra-Parenchymal Cooling Probe in Hypothermia Treatment for Ischemia or Head Injury Patients: Theoretical Analyses

2004 ◽  
Author(s):  
Liang Zhu ◽  
Axel J. Rosengart
Keyword(s):  
Animal Model ◽  
Temperature Distribution ◽  
Cerebral Ischemia ◽  
Head Injury ◽  
Brain Tissue ◽  
Brain Ischemia ◽  
Clinical Studies ◽  
Neurological Outcome ◽  
Clinical Importance ◽  
Theoretical Analyses

Inducing hypothermia to brain tissue after brain ischemia or head injury has been demonstrated beneficial to the patients. Clinical studies have shown that even 1 or 2°C temperature reduction in brain tissue can be protective [Dietrich 1992]. On the contrary, fever-induced hyperthermia can worsen the neurological outcome in an animal model after cerebral ischemia. It is of clinical importance to understand the temperature distribution in brain during brain hypothermia.

Characteristics of reactive hyperemia in the cerebral circulation

1984 ◽  
Vol 246 (1) ◽  
pp. H52-H58 ◽  
Author(s):  
J. K. Gourley ◽  
D. D. Heistad
Keyword(s):  
Blood Flow ◽  
White Matter ◽  
Cerebral Ischemia ◽  
Gray Matter ◽  
Cerebral Circulation ◽  
Time Course ◽  
Reactive Hyperemia ◽  
Arterial Occlusion ◽  
Maximal Peak ◽  
Minimal Resistance

Reactive hyperemia has been characterized in many vascular beds, but little is known about quantitative characteristics of reactive hyperemia in the cerebral circulation. We measured velocity of blood flow and pial artery diameter to characterize the time course of reactive hyperemia and used microspheres to study regional blood flow in the brain. Cerebral ischemia was produced by raising intracranial pressure or by arterial occlusion with a cuff around the neck. Five seconds of ischemia produced virtually maximal peak reactive hyperemia, and 30 s of ischemia produced maximal peak reactive hyperemia. During reactive hyperemia after 30 s of cerebral ischemia, there was a three- to fourfold increase in cerebral blood flow. The magnitude of reactive hyperemia was greater in gray matter than in white matter. Minimal resistance during reactive hyperemia, after ischemia produced by arterial occlusion, is similar to minimal resistance during seizures or hypercapnia, which suggests that reactive hyperemia produces maximal vasodilatation. Oxygen saturation of cerebral venous blood increased almost twofold during reactive hyperemia, which indicates that factors in addition to venous (and presumably tissue) oxygen are important determinants of reactive hyperemia. In summary, 1) we have characterized the time course of reactive hyperemia in the cerebral circulation; 2) reactive hyperemia after arterial occlusion produces maximal cerebral vasodilatation; and 3) there is marked heterogeneity of the response, with much larger increases in flow in cortical gray matter than white matter.

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