Research Center for High Altitude Medicine, Qinghai University, Xining, China; Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Loint Research Key Lab for High Altitude Medicine), Xining, China; Qinghai Provincial People's Hospital, Xining, China.
Qinghai Provincial People's Hospital, Xining, China.
Brain Res. 2019 Nov 15;1723:146388. doi: 10.1016/j.brainres.2019.146388. Epub 2019 Aug 14.
This study was designed to investigate whether immunomodulation and Microglia polarization is involved in the anti-inflammatory and neuroprotective effect induced by hypoxic preconditioning (HPC) in the middle cerebral artery occlusion (MCAO) brain injury model.
Longa method, (neurological disability status scale) NDSS method and TTC staining were used to evaluate the degree of cerebral infarction injury under different treatments (Sham, HPC, MCAO and co-treatment with HPC and MCAO). Western blot was used to detect expression profiles of apoptosis and related factors of neurological function. Flow cytometry was performed to analyze changes in the ratio of helper T cells, toxic T cells and NK cells in peripheral immune cells. And immunohistochemistry was used to examine the changes in microglial morphology. ELISA was used to evaluate the levels of nerve growth factors and neurogenesis conditions. Finally, RT-PCR was determined to analyze the transformation of microglia phenotype after HPC and MCAO treatment.
MCAO dramatically induced local formation of cerebral infarction. HPC relieved MCAO-induced cerebral infarction and increased rat cognition. HPC affected activation of microglia without significantly affecting in peripheral immune cell populations. After HPC co-treatment with MCAO, the M1 phenotype of microglia was changed and there was a transformation to M2.
The treatment of HPC remarkably affected the polarization of microglia cells in MCAO rats, and reduced the cerebral nerve injury and played a protective role in MCAO model.
本研究旨在探讨免疫调节和小胶质细胞极化是否参与缺氧预处理（HPC）诱导的大脑中动脉闭塞（MCAO）脑损伤模型中的抗炎和神经保护作用。
采用 Longa 法、（神经功能缺损评分量表）NDSS 法和 TTC 染色评价不同处理（假手术、HPC、MCAO 和 HPC 与 MCAO 共同处理）下脑梗死损伤程度。Western blot 检测凋亡和神经功能相关因子的表达谱。流式细胞术分析外周免疫细胞中辅助性 T 细胞、毒性 T 细胞和 NK 细胞比例的变化。免疫组织化学检测小胶质细胞形态变化。ELISA 评估神经生长因子水平和神经发生情况。最后，通过 RT-PCR 分析 HPC 和 MCAO 处理后小胶质细胞表型的转化。
MCAO 明显诱导局部脑梗死形成。HPC 减轻 MCAO 诱导的脑梗死并改善大鼠认知。HPC 影响小胶质细胞的激活，而对外周免疫细胞群没有明显影响。HPC 与 MCAO 共同处理后，小胶质细胞的 M1 表型发生变化，并向 M2 转化。
HPC 处理显著影响 MCAO 大鼠小胶质细胞的极化，减轻脑神经损伤，在 MCAO 模型中发挥保护作用。
