Voronina T A, Kraineva V A, Zolotov N N, Kotel'nikova S O, Val'dman E A
Zakusov Institute of Pharmacology, Moscow, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2022;122(8. Vyp. 2):65-71. doi: 10.17116/jnevro202212208265.
Identification of the role of oxidative stress in the development of disorders that occur in hemorrhagic stroke (HS, post-traumatic intracerebral hematoma), and the study of the effects of Mexidol on neurological and cognitive deficits in HS with an analysis of the relationship between the therapeutic effects of the drug in HS with its antioxidant effect.
The study was carried out on mature outbred male rats weighing 260-280 g. HS was created by destruction of the brain tissue in the area of the , with the introduction of blood into the site of injury. On the 1, 7, and 14 days after HS modeling, death, neurological deficits (McGrow scale, rotating rod), convulsive manifestations, and cognitive impairment were recorded in rats; blood plasma and homogenates of the cerebral cortex of rats. Mexidol was administered after the HS operation: first at a dose of 150 mg/kg, intraperitoneally, for 3 days and then 75 mg/kg, orally (from the 4 to the 14 day).
Mexidol in rats with HS significantly increases the survival rate of animals, reduces the manifestations of neurological deficits according to the McGrow scale (playpen movements, paresis of 1-4 limbs, paralysis of the lower limbs, lateral position), eliminates individual motor convulsive manifestations, restores impaired coordination of movements (rotating rod test) and improves, impaired HS, learning and memory processes. Mexidol normalizes the concentration of TBA-active products in the blood of animals and homogenates of the cerebral cortex of rats, both a day and 7 days after HS modeling.
The data obtained indicate the involvement of oxidative stress as a chain of pathogenesis in the development of disorders in HS and the ability of Mexidol to alleviate neurological deficits, convulsive manifestations and cognitive impairment in HS, which is accompanied by a decrease in oxidative stress. All this justifies the importance of the use of Mexidol in patients with hemorrhagic stroke, posttraumatic intracerebral hematoma and determines the features of its therapeutic effects.
确定氧化应激在出血性中风（HS，创伤后颅内血肿）所发生疾病发展中的作用，并研究美西多芬对HS患者神经和认知功能缺损的影响，同时分析该药物在HS中的治疗效果与其抗氧化作用之间的关系。
本研究以体重260 - 280克的成熟远交系雄性大鼠为实验对象。通过破坏大脑特定区域的脑组织并向损伤部位注入血液来制造HS模型。在HS建模后的第1、7和14天，记录大鼠的死亡情况、神经功能缺损（麦格劳评分、转棒试验）、惊厥表现和认知障碍；采集大鼠的血浆和大脑皮质匀浆。HS手术后给予美西多芬：首先以150毫克/千克的剂量腹腔注射，持续3天，然后从第4天至第14天以75毫克/千克的剂量口服。
美西多芬可显著提高HS大鼠的存活率，根据麦格劳评分降低神经功能缺损的表现（在围栏中的活动、1 - 4肢轻瘫、下肢麻痹、侧卧），消除个体运动性惊厥表现，恢复受损的运动协调性（转棒试验），并改善HS所致的学习和记忆过程受损情况。在HS建模后的第1天和第7天，美西多芬可使动物血液和大鼠大脑皮质匀浆中TBA活性产物的浓度恢复正常。
所获得的数据表明氧化应激作为发病机制链参与了HS疾病的发展，且美西多芬具有减轻HS患者神经功能缺损、惊厥表现和认知障碍的能力，同时伴有氧化应激减轻。所有这些都证明了美西多芬在出血性中风、创伤后颅内血肿患者中应用的重要性，并确定了其治疗效果的特点。
