[Study of the effect of Unifuzol on cognitive impairment and damage to the hippocampus and cerebral cortex during course administration to rats with bilateral stenosis of the common carotid arteries, causing chronic circulatory failure].

D V Kurkin, D A Bakulin, E I Morkovin, I A Myagkova, E V Kuznetsova, A S Tarasov, M V Shmidt, A I Robertus, A L Kovalenko, N A Lycheva
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Abstract

Objective: To study the effect of Unifuzol (L-arginine sodium succinate) on cognitive impairment, cerebral blood flow, and damage to the tissues of the hippocampus and cerebral cortex during a 10-day course of administration to rats with chronic cerebral ischemia (CCI) caused by bilateral stenosis of the common carotid arteries (CCA).

Material and methods: The study was conducted on male rats with CCI caused by bilateral stenosis of the CCA by 60%. 40 days after surgery, rats received Unifusol (21, 42 and 84 ml/kg), nicergoline (10 mg/kg), citicoline (500 mg/kg) or placebo (0.9% NaCl) for 10 days. Next, cognitive impairments were assessed in the Morris Water Maze and the New Object Recognition (NOR) test, as well as the level of motor and exploratory activity in the Open Field test. The level of cerebral blood flow was determined immediately after the CCA stenosis and at the end of the experiment. Animals were euthanized in a CO2 incubator, after which the brain was removed and subjected to morphometric analysis.

Results: In animals that were modeled with CCA stenosis, pronounced behavioral and cognitive impairments occurred as a result of a decrease in blood flow in the vessels of the brain and subsequent changes in the tissues of the hippocampus and the cerebral cortex. Intravenous course administration of Unifuzol at doses of 42 and 84 ml/kg to animals with CCI was comparable in efficiency to nicergoline and citicoline, which was expressed in greater preservation of the cognitive abilities of animals in the Morris Water Maze and NOR tests. In the Open Field test, animals injected with Unifusol at doses of 42 and 84 ml/kg performed more acts of motor and exploratory activity than animals from the placebo group, and had a higher level of cerebral blood flow (compared to animals that were injected with citicoline). Based on the results of a morphological study, it was found that the most significant neuroprotective effect was provided by nicergoline and Unifuzol (at doses of 42 and 84 ml/kg).

Conclusion: Unifuzol at a course of administration at doses of 42 and 84 ml/kg, comparable to the reference drugs nicergoline and citicoline, reduces the severity of psychoneurological deficit in animals with CCI, comparable to them improves the microcirculation of brain tissues, preventing damage to brain tissues.

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[Unifuzol对双侧颈总动脉狭窄致慢性循环衰竭大鼠认知功能障碍及海马、大脑皮质损伤的影响研究]。
目的:研究乌福唑(l -精氨酸琥珀酸钠)对双侧颈总动脉狭窄致慢性脑缺血(CCI)大鼠认知功能障碍、脑血流量及海马和大脑皮质组织损伤的影响。材料与方法:以60%双侧CCA狭窄致CCI的雄性大鼠为研究对象。术后40 d,大鼠分别给予uniifusol(21、42和84 ml/kg)、nicergoline (10 mg/kg)、胞胆碱(500 mg/kg)或安慰剂(0.9% NaCl)治疗10 d。接下来,通过Morris水迷宫和新物体识别(NOR)测试评估认知障碍,以及在开放领域测试中评估运动和探索活动水平。在CCA狭窄发生后立即及实验结束时测定脑血流水平。动物在二氧化碳培养箱中被安乐死,之后大脑被移除并进行形态计量学分析。结果:在用CCA狭窄建模的动物中,由于大脑血管血流减少以及随后海马和大脑皮层组织的变化,出现了明显的行为和认知障碍。对患有CCI的动物静脉给予剂量为42和84 ml/kg的Unifuzol的效率与nicergoline和citicoline相当,这在Morris水迷宫和NOR试验中表现为更大程度上保留了动物的认知能力。在Open Field试验中,与安慰剂组相比,以42和84 ml/kg剂量注射uniifusol的动物表现出更多的运动和探索活动,并且具有更高水平的脑血流量(与注射胞胆碱的动物相比)。形态学研究结果显示,尼麦角林和乌尼呋唑(剂量分别为42和84 ml/kg)的神经保护作用最为显著。结论:Unifuzol在42和84 ml/kg的给药剂量下,与对照药nicergoline和citicoline相当,可减轻CCI动物精神神经功能障碍的严重程度,改善脑组织微循环,防止脑组织损伤。
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Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova Medicine-Psychiatry and Mental Health
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