Gao Baobing, Deng Jing, Zhang Xiaogang, Sun Houchao, Jia Gongwei, Li Jiani, Zhang Keming, Wan Chengqun, Wang Linxi, Yan Liang-Jun, Cai Zhiyou, Ma Jingxi
Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400013, China; Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing, 400013, China.
Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Neurosci Lett. 2020 Jan 10;715:134657. doi: 10.1016/j.neulet.2019.134657. Epub 2019 Nov 27.
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum stress-related protein that exhibits neuroprotective effects. Recent studies have shown that MANF promotes poststroke functional recovery in rats. However, the underlying mechanisms have not yet been fully understood. Here, we examined the effects of MANF on cerebral angiogenesis in a permanent middle cerebral artery occlusion model in rats. Recombinant human MANF was administered intracerebroventricularly 24 h after stroke. We performed neurobehavioral tests and assessed microvessel density, functional microvessels, and regional cerebral blood flow (rCBF), as well as detected angiogenic factors in the peri-infarct cerebral cortex. Results showed that MANF ameliorated neurobehavioral scores, promoted rCBF, upregulated the expression of CD34, as well as the total vessel surface area and the number of microvessel branch points, and activated the vascular endothelial growth factor (VEGF) pathway. In conclusion, our findings provide insight into the mechanisms of MANF in promoting functional recovery from ischemic stroke. Our results suggest that MANF improves neurobehavioral recovery from cerebral ischemic injury, and that this effect is mediated partly by its proangiogenic effects and augmentation of rCBF, which are possibly associated with VEGF.
中脑星形胶质细胞源性神经营养因子（MANF）是一种具有神经保护作用的内质网应激相关蛋白。最近的研究表明，MANF可促进大鼠中风后功能恢复。然而，其潜在机制尚未完全明确。在此，我们在大鼠永久性大脑中动脉闭塞模型中研究了MANF对脑内血管生成的影响。中风后24小时经脑室内给予重组人MANF。我们进行了神经行为测试，并评估了微血管密度、功能性微血管、局部脑血流量（rCBF），同时检测了梗死灶周围大脑皮质中的血管生成因子。结果显示，MANF改善了神经行为评分，促进了rCBF，上调了CD34的表达以及微血管总面积和微血管分支点数，并激活了血管内皮生长因子（VEGF）通路。总之，我们的研究结果为MANF促进缺血性中风功能恢复的机制提供了见解。我们的结果表明，MANF可改善脑缺血损伤后的神经行为恢复，且这种作用部分是由其促血管生成作用和rCBF增加介导的，这可能与VEGF有关。
