Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, USA.
CNS Neurosci Ther. 2024 Feb;30(2):e14346. doi: 10.1111/cns.14346. Epub 2023 Jul 12.
Ischemic stroke (IS) is a cerebrovascular disease with high incidence and mortality. White matter repair plays an important role in the long-term recovery of neurological function after cerebral ischemia. Neuroprotective microglial responses can promote white matter repair and protect ischemic brain tissue.
The aim of this study was to investigate whether hypoxic postconditioning (HPC) can promote white matter repair after IS, and the role and mechanism of microglial polarization in white matter repair after HPC treatment.
MATERIALS & METHODS: Adult male C57/BL6 mice were randomly divided into three groups: Sham group (Sham), MCAO group (MCAO), and hypoxic postconditioning group (HPC). HPC group were subjected to 45 min of transient middle cerebral artery occlusion (MCAO) immediately followed by 40 min of HPC.
The results showed that HPC reduced the proinflammatory level of immune cells. Furthermore, HPC promoted the transformation of microglia to anti-inflammatory phenotype on the third day after the procedure. HPC promoted the proliferation of oligodendrocyte progenitors and increased the expression of myelination-related proteins on the 14th day. On the 28th day, HPC increased the expression of mature oligodendrocytes, which enhanced myelination. At the same time, the motor neurological function of mice was restored.
During the acute phase of cerebral ischemia, the function of proinflammatory immune cells was enhanced, long-term white matter damage was aggravated, and motor sensory function was decreased.
HPC promotes protective microglial responses and white matter repair after MCAO, which may be related to the proliferation and differentiation of oligodendrocytes.
缺血性脑卒中（IS）是一种发病率和死亡率都很高的脑血管疾病。白质修复在脑缺血后神经功能的长期恢复中起着重要作用。神经保护小胶质细胞反应可以促进白质修复和保护缺血性脑组织。
本研究旨在探讨低氧后处理（HPC）是否能促进 IS 后的白质修复，以及小胶质细胞极化在 HPC 治疗后白质修复中的作用和机制。
成年雄性 C57/BL6 小鼠随机分为三组：假手术组（Sham）、大脑中动脉闭塞组（MCAO）和低氧后处理组（HPC）。HPC 组在短暂性大脑中动脉闭塞（MCAO） 45 min 后立即进行 40 min 的 HPC。
结果表明，HPC 降低了免疫细胞的促炎水平。此外，HPC 促进了小胶质细胞在术后第 3 天向抗炎表型的转化。HPC 促进少突胶质前体细胞的增殖，并增加了第 14 天髓鞘相关蛋白的表达。在第 28 天，HPC 增加了成熟少突胶质细胞的表达，从而增强了髓鞘形成。同时，小鼠的运动神经功能得到恢复。
在脑缺血的急性期，促炎免疫细胞的功能增强，长期白质损伤加重，运动感觉功能下降。
HPC 促进 MCAO 后保护性小胶质细胞反应和白质修复，这可能与少突胶质细胞的增殖和分化有关。
