Hypoxic postconditioning promotes neurogenesis by modulating the metabolism of neural stem cells after cerebral ischemia
Hypoxic postconditioning promotes neurogenesis by modulating the metabolism of neural stem cells after cerebral ischemia
复制标题
低氧后处理通过调节脑缺血后神经干细胞的代谢促进神经发生
DOI：
10.1016/j.expneurol.2021.113871
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发表时间：
2021-09-29
影响因子：
5.3
通讯作者：
Jin, Kunlin
中科院分区：
文献类型：
--
作者：
Li, Haiyan;Li, Sijie;Jin, Kunlin
缺血性脑卒中是最致命、最严重致残的疾病之一，严重影响人类健康和生活质量。神经干细胞自我更新和分化的维持与新陈代谢密切相关。本研究旨在探讨低氧后处理（HPC）是否可以促进缺血性中风后的神经发生，并探讨神经元干细胞代谢在HPC诱导的神经保护中的作用。对雄性C57BL/6小鼠进行短暂大脑中动脉闭塞（MCAO），每天进行3小时的HPC。使用免疫荧光染色来评估神经发生。细胞系 NE-4C 用于阐明神经元干细胞在 21% O2 或 8% O2 中的增殖。 HPC 在第 14 天促进小鼠神经功能的恢复。在第 7 天，HPC 促进室下区 (SVZ) 的神经元前体增殖，并在第 14 天增强基底神经节和皮层的神经元前体迁移。在有或没有 HPC 的 MCAO 后，SVZ 中神经干细胞的脂肪酸氧化 (FAO) 和糖酵解发生变化。 HPC 促进 NE-4C 干细胞增殖，减少FAO并增加糖酵解。使用FAO激活剂或糖酵解抑制剂消除了HPC的所有这些有益作用。总之，脑缺血调节神经干细胞的FAO和糖酵解。 HPC促进MCAO后神经干细胞的增殖和迁移，这些作用可能与代谢的调节有关，包括FAO和糖酵解。
Ischemic stroke is one of the most lethal and severely disabling diseases that seriously affects human health and quality of life. The maintenance of self-renewal and differentiation of neural stem cells are closely related to metabolism. This study aimed to investigate whether hypoxic postconditioning (HPC) could promote neurogenesis after ischemic stroke, and to investigate the role of neuronal stem cell metabolism in HPC-induced neuroprotection. Male C57BL/6 mice were subjected to transient middle cerebral artery occlusion (MCAO), and HPC was performed for 3 h per day. Immunofluorescence staining was used to assess neurogenesis. The cell line NE-4C was used to elucidate the proliferation of neuronal stem cells in 21% O2 or 8% O2. HPC promoted the recovery of neurological function in mice on day 14. HPC promoted neuronal precursor proliferation in the subventricular zone (SVZ) on day 7 and enhanced neuronal precursor migration in the basal ganglia and cortex on day 14. Fatty acid oxidation (FAO) and glycolysis of neural stem cells in the SVZ changed after MCAO with or without HPC. HPC promoted the proliferation of NE-4C stem cells, decreased FAO and increased glycolysis. All these beneficial effects of HPC were ablated by the application of an FAO activator or a glycolysis inhibitor. In conclusion, cerebral ischemia modulated the FAO and glycolysis of neural stem cells. HPC promoted the proliferation and migration of neural stem cells after MCAO, and these effects may be related to the regulation of metabolism, including FAO and glycolysis.