Zhao Xue, Zhu Junde, Chen Shan, Liu Ruojing, Long Tingting
Department of Human Anatomy, School of Basic Medicine, Guizhou Medical University, Guiyang, People's Republic of China.
J Inflamm Res. 2023 Jul 24;16:3079-3092. doi: 10.2147/JIR.S414121. eCollection 2023.
To investigate the effect of neural stem cell-derived exosomes (NSC-Exos) on neural function after rat cerebral ischemia-reperfusion injury by regulating microglia-mediated inflammatory response.
SD rats were randomly divided into Sham group, IRI group, PBS group and NSC-Exos group. Each group was divided into 1d, 3d, 7d and 14d subgroups. In the Sham group, only cervical vessels were isolated without blockage. MCAO model was constructed in the other three groups by blocking middle cerebral artery with thread embolism. PBS group and NSC-Exos group were, respectively, injected into the lateral ventricle of PBS and Exos. Neurobehavioral deficit scores were performed for each subgroup at relative time points, then brains were taken for TTC staining, parietal cortex histopathology and microglia-mediated inflammatory response-related factors were detected.
Compared with Sham group, neurological defect score and infarction volume in both the IRI and PBS groups were significantly increased. The exploration target quadrant time and escape latency time of maze test were increased. The number of CD86/Iba1 double-positive cells increased, while CD206/Iba1 double-positive cells decreased. The expressions of IL-6 and CD86 in parietal cortex were increased, while the expressions of Arg1 and CD206 were decreased. Compared with the IRI group and PBS group, neurological defect score and infarction volume in NSC-Exos group were decreased. The exploration target quadrant time and escape latency time of water maze test were decreased. The number of CD206/Iba1 double-positive cells increased, while CD86/Iba1 double-positive cells decreased. The expressions of Arg1 and CD206 in parietal cortex were increased, while the expressions of IL-6 and CD86 were decreased.
NSC-Exos can promote the polarization of microglia, that is, inhibit the polarization of M1 and promote polarization of M2, reduce microglia-mediated neuroinflammation, suggesting that NSC-Exos may be a strategy for the treatment of microglia-mediated neuroinflammation after ischemic brain injury.
通过调节小胶质细胞介导的炎症反应，研究神经干细胞衍生外泌体（NSC-Exos）对大鼠脑缺血再灌注损伤后神经功能的影响。
将SD大鼠随机分为假手术组、缺血再灌注损伤组（IRI组）、磷酸盐缓冲液组（PBS组）和NSC-Exos组。每组再分为1天、3天、7天和14天亚组。假手术组仅分离颈血管不进行阻断。其他三组采用线栓法阻断大脑中动脉构建脑缺血再灌注损伤模型。PBS组和NSC-Exos组分别向侧脑室注射磷酸盐缓冲液和外泌体。在相对时间点对各亚组进行神经行为缺陷评分，然后取脑进行TTC染色，检测顶叶皮质组织病理学及小胶质细胞介导的炎症反应相关因子。
与假手术组相比，IRI组和PBS组的神经功能缺损评分及梗死体积均显著增加。迷宫试验的探索目标象限时间和逃避潜伏期延长。CD86/Iba1双阳性细胞数量增加，而CD206/Iba1双阳性细胞数量减少。顶叶皮质中白细胞介素-6（IL-6）和CD86的表达增加，而精氨酸酶1（Arg1）和CD206的表达减少。与IRI组和PBS组相比，NSC-Exos组的神经功能缺损评分及梗死体积降低。水迷宫试验的探索目标象限时间和逃避潜伏期缩短。CD206/Iba1双阳性细胞数量增加，而CD86/Iba1双阳性细胞数量减少。顶叶皮质中Arg1和CD206的表达增加，而IL-6和CD86的表达减少。
NSC-Exos可促进小胶质细胞极化，即抑制M1极化并促进M2极化，减轻小胶质细胞介导的神经炎症，提示NSC-Exos可能是治疗缺血性脑损伤后小胶质细胞介导的神经炎症的一种策略。
