scholarly journals METHODS FOR ESTIMATING NEUROLOGICAL DISTURBANCES IN EXPERIMENTAL CEREBRAL ISCHEMIA

Biomeditsina ◽  
2019 ◽  
pp. 69-74
Author(s):  
E. I. Bon ◽  
N. Ye. Maksimovich

Investigation of the brain pathology in experimental ischemia requires adequate methods for assessing the neurological deficit that occurs in laboratory animals, including sensory-based and behavioural disorders. In this research, we aimed to compare motor and behavioural disorders in rats with partial and subtotal experimental cerebral ischemia. The rats modelled with cerebral ischemia are found to exhibit a decrease in muscle strength, resistance to hypoxia, motor and emotional activity. The animals with incomplete cerebral ischemia demonstrated more pronounced sensory-based motor and behavioural disorders compared both with those modelled with partial cerebral ischemia and, in particular, with the control group.

2021 ◽  
pp. e529
Author(s):  
Lizaveta Bon ◽  
Nataliya Ye. Maksimovich

Objectives. It  was to assess the degree of neurological deficit in rats with cerebral ischemia and administration of omega-3 polyunsaturated fatty acids. Methods. The experiments were carried out on 42 male outbred white rats weighing 260 ± 20 g. Modeling of cerebral ischemia was carried out under conditions of intravenous thiopental anesthesia (40-50 mg / kg). The studies used models of subtotal, partial and stepwise subtotal cerebral ischemia. The table shows the experimental groups and the number of animals in them. Subtotal cerebral ischemia (SCI) was modeled by simultaneous ligation of both common carotid arteries (CCA). Partial cerebral ischemia (PCI) was modeled by ligating one CCA on the right. Stepwise subtotal CI (SSCI) was performed by sequential ligation of both CCA with an interval of 1 day (subgroup 1), 3 days (subgroup 2), or 7 days (subgroup 3). To study the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA), animals with CI were injected intragastrically with the drug "Omegamed" (SCI+ω-3 PUFA) at a dose of 5 g / kg body weight for a week. The control group consisted of sham-operated rats of the same sex and weight. Neurological deficits were assessed in the "muscle strength", "swimming test" and "open field" tests after 5-6 hours of the ischemic period. Results. With a stepwise bilateral ligation of both common carotid arteries with an interval of 1 day, neurological disorders were most pronounced, which indicates an aggravation of neurological deficit with a reduction in the time between CCA dressings. In rats with SCI, the changes were more pronounced than with PCI, but less than with SCI. The least pronounced changes were noted in the 3rd subgroup (the interval between CCA dressings was 7 days). Studies have shown the dependence of the severity of brain damage in SSCI on the interval between the cessation of blood flow in both CCA. At a 7-day interval between CCA dressings, compensatory mechanisms were activated, which prevented the development of morphological changes and neurological deficits. When CCA was ligated with an interval of 1 day, the degree of neurological deficit was maximal, which indicates insufficient implementation of compensatory mechanisms. Compared with the control group, the rats of the "SCI+ω3-PUFA" group retained neurological deficit, the muscle strength indicator was 86% less (p<0.05), the swimming duration - by 63% (p<0.05), the number of crossed squares - by 55% (p<0.05), the number of washes - by 62% (p<0.05), the number of racks - by 62.5% (p<0.05) and the number of bowel movements - by 60% (p<0.05). However, in comparison with the SCI group, the neurological deficit was less pronounced. There was an increase in muscle strength by 67% (p<0.05), swimming duration by 37.5% (p<0.05) and the number of squares crossed in the open field test by 31% (p<0.05), which indicates the presence of a corrective action in the ω3-PUFA preparation. Conclusion. The introduction of the preparation of ω-3 polyunsaturated fatty acids has a corrective effect in conditions of subtotal cerebral ischemia, contributing to a lesser severity of manifestations of neurological deficit (an increase in muscle strength, duration of swimming and the number of squares crossed in the open field test).   Key words: cerebral ischemia, rats, neurological deficiency, omega-3 polyunsaturated fatty acids.


2021 ◽  
Vol 2 (8) ◽  
pp. 01-06
Author(s):  
Lizaveta I. Bon ◽  
Maksimovich N.Yе.

Objectives: It was to assess vasoprotective effects of ω-3 polyunsaturated fatty acids in cerebral ischemia. Materials and methods: The experiments were carried out on 42 male outbred white rats weighing 260 ± 20 g. modeling of cerebral ischemia was carried out under conditions of intravenous thiopental anesthesia (40-50 mg / kg). The studies used models of subtotal, partial and stepwise subtotal cerebral ischemia. The table shows the experimental groups and the number of animals in them. Subtotal cerebral ischemia (SCI) was modeled by simultaneous ligation of both common carotid arteries (CCA). Partial cerebral ischemia (PCI) was modeled by ligating one CCA on the right. Stepwise subtotal CI (SSCI) was performed by sequential ligation of both CCA with an interval of 1 day (subgroup 1), 3 days (subgroup 2), or 7 days (subgroup 3). To study the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA), animals with CI were injected intragastrically with the drug "Omegamed" (SCI+ω-3 PUFA) at a dose of 5 g / kg body weight for a week. The control group consisted of sham-operated rats of the same sex and weight. Neurological deficits were assessed in the "muscle strength", "swimming test" and "open field" tests after 5-6 hours of the ischemic period. The study was carried out 6 hours after the simulation of the CI. Quantitative continuous data were obtained, which were processed using the licensed computer program Statistica 10.0 for Windows (StatSoft, Inc., USA). Since the experiment used small samples that had an abnormal distribution, the analysis was carried out by methods of nonparametric statistics. Data are presented as Me (LQ; UQ), where Me is the median, LQ is the value of the lower quartile; UQ is the upper quartile value. Differences between groups were considered significant at p <0.05 (Regression Model). Results: With a stepwise bilateral ligation of both common carotid arteries with an interval of 1 day, neurological disorders were most pronounced, which indicates an aggravation of neurological deficit with a reduction in the time between CCA dressings. In rats with SCI, the changes were more pronounced than with PCI, but less than with SCI. The least pronounced changes were noted in the 3rd subgroup (the interval between CCA dressings was 7 days). Studies have shown the dependence of the severity of brain damage in SSCI on the interval between the cessation of blood flow in both CCA. At a 7-day interval between CCA dressings, compensatory mechanisms were activated, which prevented the development of morphological changes and neurological deficits. When CCA was ligated with an interval of 1 day, the degree of neurological deficit was maximal, which indicates insufficient implementation of compensatory mechanisms. Compared with the control group, the rats of the "SCI+ω3-PUFA" group retained neurological deficit, the muscle strength indicator was 86% less (p<0.05), the swimming duration - by 63% (p<0.05), the number of crossed squares - by 55% (p<0.05), the number of washes - by 62% (p<0.05), the number of racks - by 62.5% (p<0.05) and the number of bowel movements - by 60% (p<0.05). However, in comparison with the SCI group, the neurological deficit was less pronounced. There was an increase in muscle strength by 67% (p<0.05), swimming duration by 37.5% (p<0.05) and the number of squares crossed in the open field test by 31% (p<0.05), which indicates the presence of a corrective action in the ω-3 polyunsaturated fatty acids preparation. Conclusion: The introduction of the preparation of ω-3 polyunsaturated fatty acids has a corrective effect in conditions of subtotal cerebral ischemia, contributing to a lesser severity of manifestations of neurological deficit (an increase in muscle strength, duration of swimming and the number of squares crossed in the open field test).


2020 ◽  
Vol 23 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Esra Cakir ◽  
Ufuk Cakir ◽  
Cuneyt Tayman ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.


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 ◽  
...  

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.


Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1722 ◽  
Author(s):  
Mark B. Plotnikov ◽  
Galina A. Chernysheva ◽  
Oleg I. Aliev ◽  
Vera I. Smol’iakova ◽  
Tatiana I. Fomina ◽  
...  

c-Jun N-terminal kinase (JNK) is activated by various brain insults and is implicated in neuronal injury triggered by reperfusion-induced oxidative stress. Some JNK inhibitors demonstrated neuroprotective potential in various models, including cerebral ischemia/reperfusion injury. The objective of the present work was to study the neuroprotective activity of a new specific JNK inhibitor, IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt), in the model of global cerebral ischemia (GCI) in rats compared with citicoline (cytidine-5′-diphosphocholine), a drug approved for the treatment of acute ischemic stroke and to search for pleiotropic mechanisms of neuroprotective effects of IQ-1S. The experiments were performed in a rat model of ischemic stroke with three-vessel occlusion (model of 3VO) affecting the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. After 7-min episode of GCI in rats, 25% of animals died, whereas survived animals had severe neurological deficit at days 1, 3, and 5 after GCI. At day 5 after GCI, we observing massive loss of pyramidal neurons in the hippocampal CA1 area, increase in lipid peroxidation products in the brain tissue, and decrease in local cerebral blood flow (LCBF) in the parietal cortex. Moreover, blood hyperviscosity syndrome and endothelial dysfunction were found after GCI. Administration of IQ-1S (intragastrically at a dose 50 mg/kg daily for 5 days) was associated with neuroprotective effect comparable with the effect of citicoline (intraperitoneal at a dose of 500 mg/kg, daily for 5 days).The neuroprotective effect was accompanied by a decrease in the number of animals with severe neurological deficit, an increase in the number of animals with moderate degree of neurological deficit compared with control GCI group, and an increase in the number of unaltered neurons in the hippocampal CA1 area along with a significant decrease in the number of neurons with irreversible morphological damage. In rats with IQ-1S administration, the LCBF was significantly higher (by 60%) compared with that in the GCI control. Treatment with IQ-1S also decreases blood viscosity and endothelial dysfunction. A concentration-dependent decrease (IC50 = 0.8 ± 0.3 μM) of tone in isolated carotid arterial rings constricted with phenylephrine was observed after IQ-1S application in vitro. We also found that IQ-1S decreased the intensity of the lipid peroxidation in the brain tissue in rats with GCI. 2.2-Diphenyl-1-picrylhydrazyl scavenging for IQ-1S in acetonitrile and acetone exceeded the corresponding values for ionol, a known antioxidant. Overall, these results suggest that the neuroprotective properties of IQ-1S may be mediated by improvement of cerebral microcirculation due to the enhanced vasorelaxation, beneficial effects on blood viscosity, attenuation of the endothelial dysfunction, and antioxidant/antiradical IQ-1S activity.


2017 ◽  
Vol 4 ◽  
pp. 105-111
Author(s):  
I.F. Belenichev ◽  
S.V. Pavlov ◽  
N.V. Bukhtiayarova ◽  
I.B. Samura ◽  
A.N. Egorov ◽  
...  

Author(s):  
N. Inhula

In the article the features of bioelectric activity and magnetic resonance imaging of the brain in patients with chronic cerebral ischemia (CCI) are exposed on the background of stable angina of the voltage ІІ and ІІІ ФК. 90 subjects (61 men and 29 women) (mean age 60.6 ± 7.8 years) were examined in the main group and 30 persons (10 men and 20 women) (mean age 55.2.6 ± 5.5 years) control group aged 45 to 74 years. The analysis of data of the conducted complex neuroimaging examination of patients with ССI on the background of stable angina was collected and provided. Based on the data obtained using neuroimaging techniques, it has been established that in patients with CCI, against the background of stable angina, the course of the disease is associated with the risk of development of the acute cerebrovascular accident.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Mingke Song ◽  
Osama Mohamad ◽  
Xiaohuan Gu ◽  
Shipeng Wei ◽  
Ling Wei ◽  
...  

Introduction and Purpose: The striatum region of the brain supports self-repair process after experimental cerebral ischemia. Optogenetics is a temporally and spatially precise method to manipulate targeted neuronal populations. We tested whether optogenetic technique can be translated into stroke treatment by photo-stimulation of the striatum after focal cerebral ischemia. Methods: Adult male channelrhodopsin-2 (ChR2) transgenic mice were utilized, taking the advantage of that the cation channel ChR2 is abundantly expressed in the striatum. Before stroke, mice were trained 5 times per day for 3 days with a modified adhesive removal test. Mice were then subjected to the ischemic insult targeting the right sensorimotor (barrel) cortex. Four days after stroke, optical fibers were implanted into the striatum and fixed with a cannula on the skull. In control group, stoke mice received optical fiber implantation but without photo-stimulation. In treatment group, daily photo-stimulation pulses (473 nm blue laser) were started at 5 days after stroke and sustained for 8 days. The adhesive removal test on forepaws was performed 3, 10, 17, 24, and 31 days after stroke. Results: The impaired forepaw sensorimotor function in these two groups progressively recovered over the timeline. Stroke mice treated with photo-stimulation showed significantly better recovery assessed 31 days after stroke compared to stroke control. Our study also shows that the activity of neurogenesis in the brain was augmented by photo-stimulation, which may be responsible for enhanced functional recovery. Conclusions: Optogenetic stimulation of the striatum promotes functional recovery and neurogenesis after focal ischemic stroke.


2020 ◽  
Vol 66 (4) ◽  
pp. 339-344
Author(s):  
V.E. Novikov ◽  
O.S. Levchenkova

The level of erythropoietin (EPO) and vascular endothelial growth factor (VEGF-A) was investigated in blood serum and brain of Wistar rats by the enzyme immunoassay with specific rat antibodies. These growth factors are actively studied as biomarkers of ischemia or cytoprotection, as well as targets for agents initiating preconditioning (PreC). Pharmacological (amtizol administration), hypoxic (hypobaric hypoxia), and combined PreC (amtizol+hypobaric hypoxia) were used as neuroprotective approaches in this experimental work. In normoxia groups blood and brain tissue were collected 1 h (early period) or 48 h (delayed period) after the PreC. In addition we studied groups of animals with cerebral ischemia (induced by bilateral ligation of the common carotid arteries) 1 h and 48 h after the combined PreC: the levels of EPO and VEGF-A in the blood serum and the brain supernatant were determined in one day after the ligation. Experiments have shown that amtizol (3,5-diamino-1,2,4-thiadiazole) in normoxia increased the EPO level in the brain, and did not change EPO in blood serum and VEGF-A levels in both serum and the brain. A three-day (60 min exposure with 48 h intervals) hypobaric hypoxia (410 mm Hg) increased EPO and VEGF-A in the blood serum and brain tissues, but in most experimental groups differences did not reach the level of statistical significance versus intact control. The combined PreC was accompanied by a significant increase of EPO and VEGF-A in normoxia conditions both in early and delayed period of PreC. In cerebral ischemia the EPO level in the blood serum and brain tissues was higher than in intact control. The serum level of VEGF-A of the ischemia control group tended to increase while the brain level of VEGF-A remained basically unchanged versus the intact control group. In combined PreC before ischemia, the EPO level was lower in serum as compared with the ischemia control in the delayed PreC period, but did not differ significantly from the ischemia control in serum in early period and in brain tissues in both PreC periods. The VEGF-A level in the groups of combined PreC was significantly lower in serum as compared with the ischemia control in both the early and delayed PreC; in brain tissues it did not differ from the level of both the intact and ishemia control in early PreC period and was higher than in both control groups in the delayed PreC period.


Author(s):  
Д.А. Бакулин ◽  
Д.В. Куркин ◽  
Е.В. Волотова ◽  
Е.О. Логвинова ◽  
К.А. Авдиенко ◽  
...  

Сахарный диабет (СД) 2 типа значительно повышает риск развития инсульта и выбор гипогликемической терапии может оказать влияние не только на вероятность развития, но и на тяжесть течения нарушения мозгового кровообращения (НМК). Цель: оценить влияние комбинированного введения агониста GPR119 с метформином и цитиколином на выраженность психоневрологических нарушений у животных с НМК на фоне СД. Методика. Исследование проведено на крысах линии Wistar, которым моделировали фокальную ишемию ГМ на фоне 28 дневного стрептозотоцин-никотинамид-индуцированного СД. Агонист рецептора GPR119 (дипиарон) и его комбинацию с метформином вводили с первого дня развития СД, а цитиколин - после моделирования НМК. Психоневрологические нарушения оценивались с использованием шкал «Combs & D’Alecy» и «Garcia», и тестов «Открытое поле», «Ротарод», УРПИ и ТЭИ. Результаты и обсуждение. Введение метформина приводило к нормализации уровня гликемии, но не снижало выраженность неврологического дефицита при последующем моделировании НМК. По сравнению с контролем в группах, получавших дипиарон и в большей степени его комбинацию с метформином, помимо улучшения контроля гликемии наблюдалось значительное снижение объема инфаркта и отёка мозга, а также выраженности психоневрологических нарушений у выживших животных (p<0,05). Введение цитиколина без гипогликемической терапии не приводило к снижению уровня неврологического дефицита по сравнению с контрольной группой, при этом добавление цитиколина к гипогликемической терапии значимо не снижало тяжесть течения НМК. Заключение. Комбинированное введение агониста GPR119 и метформина животным с экспериментальной ишемией ГМ на фоне СД значительно повышает терапевтический потенциал обоих препаратов, обеспечивая лучший контроль уровня гликемии и снижая выраженность психоневрологического дефицита при моделировании НМК. Type 2 diabetes mellitus (DM2) significantly increases the risk of stroke, and the choice of hypoglycemic therapy may influence not only a probability of stroke but also severity of cerebrovascular disease. Objective: To evaluate the effect of combination treatment with a GPR119 agonist, metformin and citicoline on severity of neurological disorders in animals with stroke and diabetes. Cerebral ischemia was modeled by intraluminal occlusion of the middle cerebral artery (OMCA). Methods. The study was performed on Wistar rats with 28-day streptozotocin-nicotinamide-induced diabetes. The GPR119 receptor agonist (dipiaron) and its combination with metformin were administered starting from the first day of DM, and citicoline was administered after the induction of brain ischemia. Behavioral and neurological disorders were evaluated using the Combs & D’Alecy and Garcia scales, and the open field, Rotarod, and active and passive avoidance tests. Results. The metformin treatment normalized glycemia but did not alleviate severity of the neurological deficit induced by subsequent OMCA. The groups treated with dipiaron and its combination with metformin, in addition to improved glycemic control, showed significant decreases in brain infarction volume and edema and the severity of neurological disorders in surviving animals compared to the control (p<0.05). Administration of citicoline without the hypoglycemic therapy reduced the neurological deficit in comparison with the control group. Addition of citicoline to the hypoglycemic therapy did not significantly reduce the severity of brain ischemia. Conclusion. The combination treatment of animals with brain ischemia and diabetes with the GPR119 agonist and metformin significantly enhanced the therapeutic potential of both drugs evident as a better glycemic control and alleviated severity of the neurological deficit following OMCA.


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