脑内注射水蛭素可减轻脑缺血大鼠的认知障碍和氧化应激,并促进海马神经发生。

IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY
Neuropathology Pub Date : 2023-10-01 Epub Date: 2023-03-14 DOI:10.1111/neup.12897
Xianfeng Xia, Min Li, Renxian Wei, Jin Li, Yulin Lei, Meikui Zhang
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引用次数: 0

摘要

脑缺血始于脑血流中断,导致氧气和葡萄糖供应严重受限,引发一系列病理事件,如兴奋性毒性、氧化应激、钙失调和炎症反应,最终可能导致神经元死亡。水蛭素对缺血性中风具有有益作用,并具有抗氧化和抗炎特性。因此,我们研究了水蛭素在脑缺血中的生物学功能及其相关机制。短暂性大脑中动脉闭塞(MCAO)可诱发脑缺血样病变。为了研究水蛭素的作用,侧脑室注射10 给大鼠服用U水蛭素。认知和运动功能通过梁式步行和Morris水迷宫测试进行检查。2,3,5-三苯基氯化四氮唑染色的脑切片用于测量梗死体积。通过评估氧化应激标志物来确定氧化应激。用BrdU和Nestin双染色法对增殖的细胞进行标记。进行蛋白质印迹以测量蛋白质水平。水蛭素给药改善了缺血后的认知和运动缺陷。水蛭素可减少MCAO大鼠的脑梗死和神经损伤。水蛭素减轻了缺血大鼠的氧化应激,增强了神经发生。水蛭素促进细胞外信号调节激酶(ERK)1/2和丝氨酸-苏氨酸激酶的磷酸化。总之,水蛭素通过调节MCAO大鼠的ERK1/2和丝氨酸-苏氨酸激酶来减轻氧化应激并促进海马神经发生,从而减轻认知缺陷。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Intracerebral hirudin injection alleviates cognitive impairment and oxidative stress and promotes hippocampal neurogenesis in rats subjected to cerebral ischemia.

Cerebral ischemia starts with cerebral blood flow interruption that causes severely limited oxygen and glucose supply, eliciting a cascade of pathological events, such as excitotoxicity, oxidative stress, calcium dysregulation, and inflammatory response, which could ultimately result in neuronal death. Hirudin has beneficial effects in ischemic stroke and possesses antioxidant and anti-inflammatory properties. Therefore, we investigated the biological functions of hirudin and its related mechanisms in cerebral ischemia. The ischemia-like conditions were induced by transient middle cerebral artery occlusion (MCAO). To investigate hirudin roles, intracerebroventricular injection of 10 U hirudin was given to the rats. Cognitive and motor functions were examined by beam walking and Morris water maze tests. 2,3,5-triphenyl tetrazolium chloride-stained brain sections were used to measure infarct volume. Oxidative stress was determined by assessment of oxidative stress markers. The proliferated cells were labeled by BrdU and Nestin double staining. Western blotting was performed to measure protein levels. Hirudin administration improved cognitive and motor deficits post-ischemia. Hirudin reduced brain infarction and neurological damage in MCAO-subjected rats. Hirudin alleviated oxidative stress and enhanced neurogenesis in ischemic rats. Hirudin facilitated the promotion of phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and serine-threonine kinase. In sum, hirudin alleviates cognitive deficits by attenuating oxidative stress and promoting hippocampal neurogenesis through the regulation of ERK1/2 and serine-threonine kinase in MCAO-subjected rats.

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来源期刊
Neuropathology
Neuropathology 医学-病理学
CiteScore
4.10
自引率
4.30%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
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