scholarly journals STUDY OF CEREBROTROPIC DOSE-DEPENDENT EFFECT OF PYRIMIDINE DERIVATIVE UNDER PIR-9 CODE AGAINST THE BACKGROUND OF EXPERIMENTAL CEREBRAL ISCHEMIA IN RATS

2019 ◽  
Vol 6 (6) ◽  
pp. 548-567
Author(s):  
A. V. Voronkov ◽  
N. B. Shabanova ◽  
M. P. Voronkova ◽  
T. A. Lysenko
Keyword(s):  
Cerebral Ischemia ◽  
Carotid Arteries ◽  
Tween 80 ◽  
Pyrimidine Derivative ◽  
Behavioral Activity ◽  
Test Substance ◽  
Reference Drug ◽  
Dose Dependent ◽  
Common Carotid Arteries ◽  
Experimental Cerebral Ischemia

Nowadays, the incidence of cerebrovascular disease is steadily increasing. Disorders of cerebral circulation contribute to the increase in the degree of mortality, disability, and incapacitation of the population. An extensive arsenal of drugs with cerebroprotective effects does not satisfy clinical specialists. In this connection, there is an obvious need for new compounds exhibiting cerebroprotropic properties, as well as those able of improving the prognosis of the course of ischemic genesis pathologies.The aimof the article is to study the dose-dependent cerebrotropic effect of a pyrimidine derivative under PIR-9 code against the background of experimental cerebral ischemia in rats.Materials and methods. The experiment was conducted on 140 male Wistar rats (m=170–190 g) divided into 7 equal groups. Pyrimidine derivative PIR – 9 (25, 50 and 100 mg/kg), Vinpocetine (3.2 mg/kg) and Cinnarizine (5.6 mg/kg) suspension of purified water and Tween-80 were used as the studied substances. Experimental cerebral ischemia was reproduced by irreversible occlusion of common carotid arteries (chloral hydrate anesthesia – 350 mg/kg). Experimental substances, reference preparations and purified water were administered prophylactically within 10 days before surgery. One day later the survival, neurological deficiency, behavioral activity, changes in cognitive-mnestic functions, as well as some indicators of brain energy exchange were evaluated.Results.In an experimental study of the cerebrotropic effect of the substance under PIR-9 code (pyrimidine-4-(1H)-one derivative) in various dosages against the background of irreversible occlusion of the common carotid arteries, a decrease in neurological, behavioral, mnestic and cognitive defects has been established. Hereby, the best effect was observed against the background of the administration of the compound PIR-9 at the dose of 50 mg kg. In addition, the prophylactic administration of the test substance PIR-9 (50 mg/kg) has shown the improvement of the energy metabolism in the postischemic period.Conclusion. In the course of the study it was established that the substance under the laboratory code PIR-9 exhibited the most pronounced cerebroprotective effect at the dose of 50 mg/ kg, which was not inferior in its strength to the reference drug Cinnarizine and exceeding Vinpocetine.

scholarly journals THE EFFECT OF PIR-20 COMPOUND ON COGNITIVE DEFICIT REDUCTION IN EXPERIMENTAL GLOBAL CEREBRAL ISCHEMIA IN RATS

2021 ◽  
Vol 11 (3) ◽  
pp. 26-28
Author(s):  
Natalia Shabanova ◽  
Anastasia Gerashchenko ◽  
Andrey Voronkov
Keyword(s):  
Cerebral Ischemia ◽  
Tween 80 ◽  
Pyrimidine Derivative ◽  
Negative Control ◽  
Global Cerebral Ischemia ◽  
Control Group ◽  
Reference Drug ◽  
Deficit Reduction ◽  
Male Wistar Rats ◽  
Extrapolation Escape Test

A study was conducted to assess the effect of a new pyrimidine derivative PIR-20 (50 mg/kg) on the development of cognitive deficits in the conditions of global cerebral ischemia in rats. The study was performed on 40 male Wistar rats weighing 200–220 g, divided into 4 groups of 10 individuals. False-operated rats and negative control animals were injected with a suspension of purified water and tween-80, the third group of animals received Cavinton (3,2 mg/kg), the fourth — PIR-20 (50 mg/kg). All test subjects were injected intraperitoneally for ten days prior to surgery. The number of dives increased to 100%, while the decision-making time decreased by 55,2% (p<0,05) in the extrapolation escape test against the background of the PIR-20 compound administration. 75% of the animals treated with PIR-20 did not re-visit the dark compartment, and the time of entering the dark chamber increased by 172,9% (p<0,05) as compared to the group of negative control rats in the test of passive avoidance of the avesir environment. It was confirmed that the studied compound PIR-20 contributes to the improvement of cognitive and mnestic functions, which is confirmed by the results of tests of passive and active aversive environment avoidance. The obtained effect exceeded the results of the control group and the reference drug Cavinton.

Effect of carvedilol on the redox-status of plasma low-molecular-weight aminothyols in rats with acute cerebral ischemia

2018 ◽  
pp. 12-18
Author(s):  
К.А. Никифорова ◽  
В.В. Александрин ◽  
П.О. Булгакова ◽  
А.В. Иванов ◽  
Э.Д. Вирюс ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cerebral Ischemia ◽  
Carotid Arteries ◽  
Redox Status ◽  
Global Cerebral Ischemia ◽  
Low Molecular Weight ◽  
Adrenergic Antagonist ◽  
Acute Cerebral Ischemia ◽  
Common Carotid Arteries ◽  
Reduced Forms

Цель. Установить влияние неспецифического адреноблокатора карведилола на редокс-статус низкомолекулярных аминотиолов (цистеин, гомоцистеин, глутатион) в плазме крови при моделировании глобальной ишемии головного мозга у крыс. Методика. Нами была использована модель глобальной ишемии (пережатие общих сонных артерий с геморрагией длительностью 15 мин). Препарат вводили за 1 ч до операции. Уровни аминотиолов измеряли через 40 мин после начала реперфузии. Анализ уровня аминотиолов проводили методом жидкостной хроматографии. Результаты. Установлено, что у крыс, не подвергавшихся ишемии, карведилол в дозе 10 мг/кг вызывает рост редокс-статуса цистеина и глутатиона (в 3 и 3,5 раза соответственно по сравнению с контролем, p = 0,04 и p = 0,008) за счет увеличения их восстановленных форм. При ишемии данного эффекта не наблюдалось. Редокс-статус у крыс с ишемией на фоне карведилола (Цис = 0,85 ± 0,14%, Глн = 1,8 ± 0,7%, Гцис = 1,1 ± 0,8%) оставался таким же низким, как и у крыс с ишемией без введения карведилола (р > 0,8). Заключение. Полученный результат демонстрирует, что в условиях ишемии головного мозга карведилол не оказывает эффекта на гомеостаз аминотиолов плазмы крови, несмотря на выраженный антиоксидантный эффект в нормальных условиях. Aim. Effect of a nonspecific adrenergic antagonist carvedilol on the redox status of plasma low-molecular-weight aminothiols (cysteine, homocysteine, glutathione) was studied in rats with global cerebral ischemia (occlusion of common carotid arteries with hemorrhage). Methods. A model of global ischemia (occlusion of common carotid arteries with 15-min hemorrhage) was used. The drugs were administered one hour before the operation. Aminothiol levels were measured by HPLC with UV detection at 40 minutes after the onset of reperfusion. Results. Carvedilol 10 mg/kg increased the redox status of cysteine and glutathione in rats not exposed to ischemia (3 and 3.5 times, respectively, compared with the control, p = 0.04 and p = 0.008, respectively) but not of homocysteine, by increasing their reduced forms. However, this effect was not observed in ischemia. In rats with ischemia treated with carvedilol, the redox status (Cys = 0.85 ± 0.14%, GSH = 1.8 ± 0.7%, Hcys = 1.1 ± 0.8%) remained low similar to that in rats with ischemia not treated with carvedilol (p >0.8, 0.8, and 0.9, respectively). Conclusion. Carvedilol did not affect the homeostasis of blood plasma thiols in cerebral ischemia despite the pronounced antioxidant effect under the normal conditions.

scholarly journals Neuroprotective Effects of Bone Marrow Mesenchymal Stem Cells on Bilateral Common Carotid Arteries Occlusion Model of Cerebral Ischemia in Rat

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Bagher Pourheydar ◽  
Sara Soleimani Asl ◽  
Mostafa Azimzadeh ◽  
Adel Rezaei Moghadam ◽  
Asghar Marzban ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cerebral Ischemia ◽  
Functional Recovery ◽  
Carotid Arteries ◽  
Ischemia Reperfusion ◽  
Neuroprotective Effects ◽  
Marrow Mesenchymal Stem Cells ◽  
Common Carotid Arteries

Cell therapy is the most advanced treatment of the cerebral ischemia, nowadays. Herein, we discuss the neuroprotective effects of bone marrow mesenchymal stem cells (BMSCs) on rat hippocampal cells following intravenous injection of these cells in an ischemia-reperfusion model. Adult male Wistar rats were divided into 5 groups: control, sham (surgery without blockage of common carotid arteries), ischemia (common carotid arteries were blocked for 30 min prior to reperfusion), vehicle (7 days after ischemia PBS was injected via the tail vein), and treatment (injections of BMSC into the tail veins 7 days after ischemia). We performed neuromuscular and vestibulomotor function tests to assess behavioral function and, finally, brains were subjected to hematoxylin and eosin (H&E), anti-Brdu immunohistochemistry, and TUNEL staining. The ischemia group had severe apoptosis. The group treated with BMSCs had a lower mortality rate and also had significant improvement in functional recovery (P<0.001). Ischemia-reperfusion for 30 min causes damage and extensive neuronal death in the hippocampus, especially in CA1 and CA3 regions, leading to several functional and neurological deficits. In conclusion, intravenous injection of BMSCs can significantly decrease the number of apoptotic neurons and significantly improve functional recovery, which may be a beneficial treatment method for ischemic injuries.

scholarly journals Adenosine A2A receptor agonist polydeoxyribonucleotide ameliorates short-term memory impairment by suppressing cerebral ischemia-induced inflammation via MAPK pathway

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248689
Author(s):  
Il-Gyu Ko ◽  
Jun-Jang Jin ◽  
Lakkyong Hwang ◽  
Sang-Hoon Kim ◽  
Chang-Ju Kim ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Cytokines ◽  
Memory Impairment ◽  
Carotid Arteries ◽  
Short Term Memory ◽  
Mapk Signaling ◽  
Short Term ◽  
The Common ◽  
Common Carotid Arteries ◽  
Pro Inflammatory Cytokines

Cerebral ischemia causes tissue death owing to occlusion of the cerebral blood vessels, and cerebral ischemia activates mitogen-activated protein kinase (MAPK) and induces secretion of pro-inflammatory cytokines. Adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), suppresses the secretion of pro-inflammatory cytokines and exhibits anti-inflammatory effect. In the current study, the therapeutic effect of PDRN on cerebral ischemia was evaluated using gerbils. For the induction of cerebral ischemia, the common carotid arteries were exposed, and then aneurysm clips were used to occlude the common carotid arteries bilaterally for 7 minutes. In the PDRN-treated groups, the gerbils were injected intraperitoneally with 0.3 mL of saline containing 8 mg/kg PDRN, per a day for 7 days following cerebral ischemia induction. In order to confirm the participation of the adenosine A2A receptor in the effects mediated by PDRN, 8 mg/kg 7-dimethyl-1-propargylxanthine (DMPX), adenosine A2A receptor antagonist, was treated with PDRN. In the current study, induction of ischemia enhanced the levels of pro-inflammatory cytokines and increased phosphorylation of MAPK signaling factors in the hippocampus and basolateral amygdala. However, treatment with PDRN ameliorated short-term memory impairment by suppressing the production of pro-inflammatory cytokines and inactivation of MAPK signaling factors in cerebral ischemia. Furthermore, PDRN treatment enhanced the concentration of cyclic adenosine-3,5’-monophosphate (cAMP) as well as phosphorylation of cAMP response element-binding protein (p-CREB). Co-treatment of DMPX and PDRN attenuated the therapeutic effect of PDRN on cerebral ischemia. Based on these findings, PDRN may be developed as the primary treatment in cerebral ischemia.

scholarly journals The effect of PIR-9 compound on markers of apoptosis in experimental focal cerebral ischemia in rats

2019 ◽  
Vol 9 (1) ◽  
pp. 83-85
Author(s):  
A.V. Voronkov ◽  
N.B. Shabanova ◽  
M.P. Voronkova ◽  
T.A. Lysenko ◽  
A.V. Arlt ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Rat Brain ◽  
Focal Cerebral Ischemia ◽  
Pyrimidine Derivative ◽  
Negative Control ◽  
Reference Drug ◽  
Apoptosis Markers

A study to assess the effect of a new pyrimidine derivative (PIR-9 at a dose of 50 mg/kg) on apoptosis markers in experimental focal cerebral ischemia of the rat brain. It has been confirmed that the investigated compound PIR-9 contributes to a decrease in the concentration of TNFα by 34,36% (p<0,05) as compared to that in rats treated with a reference drug Cavinton (3,2 mg/kg) and has an effect comparable in effect to Gliatilin (60 mg/kg). The concentration of AIF in rats that received compound PIR-9 was 29,99% (p<0,05) less than the group of negative control rats.

scholarly journals al deficits in experimental global cerebral ischemia in rats

2020 ◽  
Vol 10 (4) ◽  
pp. 26-28
Author(s):  
Natalia Shabanova ◽  
Anastasia Gerashchenko ◽  
Andrey Voronkov
Keyword(s):  
Cerebral Ischemia ◽  
Brain Ischemia ◽  
Neurological Status ◽  
Pyrimidine Derivative ◽  
Neurological Deficits ◽  
Global Cerebral Ischemia ◽  
Control Group ◽  
Global Brain Ischemia ◽  
Reference Drug ◽  
Global Brain

This study was aimed to assess the effect of a new pyrimidine derivative (PIR-12 50 mg/kg) on survival and neurological deficits in rat global brain ischemia. It has been confirmed that the investigated compound PIR-12 contributes to an increase in survival up to 80% and a decrease in neurological status by 73,3% compared to the control group of animals and exceeds the strength of the effect of the reference drug Cavinton by 30% and 22,48%, respectively.

scholarly journals Histological disorders of neurons of phylogenetically different parts of the cerebral cortex in partial, subtotal, stepwise subtotal, and total cerebral ischemia

2021 ◽  
Vol 90 (1) ◽  
pp. e493
Author(s):  
Lizaveta I. Bon ◽  
Nataliya Y. Maksimovich
Keyword(s):  
Cerebral Ischemia ◽  
Carotid Artery ◽  
Parietal Cortex ◽  
Common Carotid Artery ◽  
Carotid Arteries ◽  
Morphological Changes ◽  
Oxygen Deficiency ◽  
Progressive Increase ◽  
Histological Changes ◽  
Common Carotid Arteries

Aim. Measure of the histological changes in neurons in the parietal cortex and hippocampus of rats with partial, subtotal, stepwise subtotal, and total cerebral ischemia. Material and Methods. Studies were performed on 84 rats. Partial cerebral ischemia was modelled by ligation of one common carotid artery. Subtotal cerebral ischemia was modelled by ligation of both common carotid arteries. Stepwise subtotal cerebral ischemia was performed by sequential ligation of both common carotid artery with 7-day, 3-day or 1-day intervals. Total cerebral ischemia (CI) was modelled by decapitation. Results. When comparing the morphological changes of neurons in the parietal cortex and hippocampus, we observed that, with the aggravation of the severity of cerebral ischemia, there was a progressive increase in the number of hyperchromic shrivelled neurons and neurons with pericellular oedema. Modelling of more severe types of ischemic damage lead to pronounced morphological changes in neurons – a decrease in size, deformation of the perikaryon, and increase in the degree of neuronal chromatophilia with their wrinkling. Conclusions. The smallest morphological changes in neurons were noted in the partial cerebral ischemia groups and subgroup 1 of stepwise subtotal cerebral ischemia, with an interval between common carotid artery dressings of 7 days. The most obvious morphological changes were observed in the conditions of total cerebral ischemia after 1 day. Changes in the parietal cortex and hippocampus were unidirectional, but in the parietal cortex, which is most sensitive to oxygen deficiency, they were more pronounced.

scholarly journals Experimental justifi cation and dependent eff ects of therapy by the mexicor of ischemic brain injection in rats

2019 ◽  
Author(s):  
Oleksandr Stoyanov ◽  
Ruslan Vastyanov ◽  
Olena Kolesnyk ◽  
Serhii Mashchenko ◽  
Serhii Antonenko
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Carotid Arteries ◽  
Vascular Pathology ◽  
Muscle Rigidity ◽  
Chronic Cerebral Ischemia ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Cerebrovascular Pathology ◽  
Dose Dependent

Brain vascular pathology is one of the leading causes of mortality, the main cause of disability and life quality decrease throughout the world. Ukraine demonstrate a steady tendency to increase the prevalence and incidence of cerebrovascular pathology over the past 10—15 years, especially chronic progressive forms. Oxidative stress is one of the leading ischemic brain damage cause. To suppress it the main modern approaches in cerebrovascular pathology pharmacological treatment search are connected. The use of the antioxidant 2-ethyl- 6-methyl-3-hydroxypyridine succinate as a pathogenetically necessary agent in conditions of ischemic brain damage during bilateral occlusion of the common carotid arteries in rats in order to study the eff ectiveness of therapy is experimentally substantiated in the article. 4 groups of animals were used in experimental conditions. Rats motor activity in the "open fi eld" test, trembling and stiff ness, a "humpiness" symptom, muscular activity and neurological status were determined on the 2nd, 5th, 7th, 14th and 28th days of the experimental trials. Rats after reproducing ischemia of the brain showed hypokinesia, discoordination, muscle rigidity, severe neurological defi ciency. Mexicor administered in doses of 50 mg/kg and 100 mg/kg contributed to a dose-dependent decreasing of the studied indexes. The eff ectiveness of using mexicor signifi cantly exceeded the results obtained in the group without treatment. A dose-dependent eff ect was recorded with a signifi cant diff erence with increasing dosage. Thus, behavioral, muscular, coordinative and neurological correlates of chronic cerebral ischemia induced by carotid arteries occlusion gone during 14—28 days in conditions of mexicor efficacy. The experimental results obtained are the background for a clinical examinations further series of patients with chronic cerebral ischemia using Mexicor as one of the components of ischemic brain damage complex pathogenetically based pharmacocorrection. Key words: experimental ischemia, 2-ethyl-6-methyl-3-hydroxypyridine succinate, pathogenetic treatment, ischemic brain damage pharmacocorrection

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