School of Life Sciences, South China Normal University, Guangzhou, 510631, China.
Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, 510631, China.
Sci Rep. 2020 Nov 26;10(1):20646. doi: 10.1038/s41598-020-77678-8.
Ischemic strokes cause devastating brain damage and functional deficits with few treatments available. Previous studies have shown that the ischemia-hypoxia rapidly induces clinically similar thrombosis and neuronal loss, but any resulting behavioral changes are largely unknown. The goal of this study was to evaluate motor and cognitive deficits in adult HI mice. Following a previously established procedure, HI mouse models were induced by first ligating the right common carotid artery and followed by hypoxia. Histological data showed significant long-term neuronal losses and reactive glial cells in the ipsilateral striatum and hippocampus of the HI mice. Whereas the open field test and the rotarod test could not reliably distinguish between the sham and HI mice, in the tapered beam and wire-hanging tests, the HI mice showed short-term and long-term deficits, as evidenced by the increased number of foot faults and decreased hanging time respectively. In cognitive tests, the HI mice swam longer distances and needed more time to find the platform in the Morris water maze test and showed shorter freezing time in fear contextual tests after fear training. In conclusion, this study demonstrates that adult HI mice have motor and cognitive deficits and could be useful models for preclinical stroke research.
缺血性中风会导致严重的脑损伤和功能缺陷,而目前可用的治疗方法却很少。先前的研究表明,缺血-缺氧会迅速引起临床相似的血栓形成和神经元丢失,但由此产生的任何行为变化在很大程度上尚不清楚。本研究的目的是评估成年 HI 小鼠的运动和认知缺陷。根据先前建立的程序,通过首先结扎右侧颈总动脉,然后进行缺氧处理来诱导 HI 小鼠模型。组织学数据显示,HI 小鼠的同侧纹状体和海马体中存在明显的长期神经元丢失和反应性神经胶质细胞。虽然旷场试验和转棒试验不能可靠地区分假手术和 HI 小鼠,但在渐缩棒和悬线试验中,HI 小鼠表现出短期和长期的缺陷,表现在脚误次数增加和悬挂时间减少。在认知测试中,在 Morris 水迷宫测试中,HI 小鼠游得更远的距离,找到平台所需的时间更长,在恐惧条件性测试中,恐惧训练后冻结时间更短。总之,本研究表明,成年 HI 小鼠存在运动和认知缺陷,可作为临床前中风研究的有用模型。