在食蟹猴的缺血性中风后,白质脱髓鞘早于轴突损伤。
White matter demyelination predates axonal injury after ischemic stroke in cynomolgus monkeys.
机构信息
Department of Neurology, Dalian Municipal Central Hospital affiliated with Dalian Medical University, Dalian, China.
Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangdong, China.
出版信息
Exp Neurol. 2021 Jun;340:113655. doi: 10.1016/j.expneurol.2021.113655. Epub 2021 Feb 19.
Unraveling the pathology of stroke is a prerequisite for designing therapeutic strategies. It was reported that myelin injury exceeded axonal loss in the peri-infarct region of rodent white matter stroke. An in-depth investigation of the post-stroke white matter damage in higher-order species might innovate stroke intervention. In this study, adult male cynomolgus monkeys received surgical middle cerebral artery occlusion (MCAO), and serial magnetic resonance scans to non-invasively assess brain damage. Spontaneous movements were recorded to evaluate post-stroke behavior. The axon and myelin loss, as well as immune cell infiltration were examined using immunohistochemistry. Magnetic resonance imaging revealed cerebral infarcts and white matter injury after MCAO in monkeys, which were confirmed by neurological deficits. Immunostaining of white matter fibers showed substantial demyelination whilst retention of axons in the infarcts 8 days post MCAO, while a progressive loss of myelin and axons was observed after one month. Gliosis, microglia activation, and leukocyte infiltration were identified in the lesions. These results demonstrate that demyelination predates axonal injury in non-human primate ischemic stroke, which provides a time window for stroke intervention focusing on prevention of progressive axonal loss through myelin regeneration.
解析中风的病理学是设计治疗策略的前提。据报道,在啮齿动物白质中风的梗死周边区域,髓鞘损伤超过了轴突丢失。深入研究高等级物种中风后的白质损伤可能会为中风干预带来创新。在这项研究中,成年雄性食蟹猴接受了大脑中动脉闭塞(MCAO)手术,并进行了一系列磁共振扫描,以无创评估脑损伤。记录自发性运动以评估中风后的行为。通过免疫组织化学检查轴突和髓鞘丢失以及免疫细胞浸润。磁共振成像显示猴子 MCAO 后出现脑梗死和白质损伤,神经功能缺损得到证实。白质纤维的免疫染色显示,在 MCAO 后 8 天梗死区出现明显的脱髓鞘,而髓鞘和轴突的丢失在一个月后逐渐出现。在病变中鉴定出神经胶质增生、小胶质细胞激活和白细胞浸润。这些结果表明,在非人类灵长类动物缺血性中风中,脱髓鞘先于轴突损伤,这为中风干预提供了一个时间窗口,重点是通过髓鞘再生预防进行性轴突丢失。