Zhou Feihui, Liu Rong, Han Pengcheng, Zhang Xingkui, Li Zhigao, Zhang Shen, Liu Chang, Xia Yang, Tang Zhiwei
Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Front Cell Neurosci. 2020 Jun 26;14:152. doi: 10.3389/fncel.2020.00152. eCollection 2020.
: To investigate the effect and the underlying mechanism of Pertussis toxin (PTX) on microglia in the setting of cerebral ischemia. : We tested the effect of PTX 400 ng/days on middle cerebral artery occlusion stroke model by evaluating the neurologic function, infarct size, microglial distribution, and activation. In parallel, we also tested the effect of PTX on primary cultured microglia by evaluating microglial proliferation, activation, cytokine release, and CX3CR1 expression. : PTX reduced the poststroke infarct size, improved the neurologic function as evaluated by Longa score, and reduced microglial aggregation and activation in the infarcted area. Further, PTX significantly decreased lipopolysaccharide-stimulated microglial proliferation, the release of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α), and the expression of CX3CR1. : PTX treatment in stroke reduced microglial accumulation and activation in the infarct zone, resulting in a better functional outcome. The benefits of PTX treatment may be attributed to the reduced production of proinflammatory cytokine such as IL-1β and TNF-α and reduced expression of chemokine CX3CR1.
研究百日咳毒素(PTX)在脑缺血情况下对小胶质细胞的作用及其潜在机制。
通过评估神经功能、梗死面积、小胶质细胞分布和激活情况,检测400 ng/天的PTX对大脑中动脉闭塞性卒中模型的影响。同时,通过评估小胶质细胞增殖、激活、细胞因子释放和CX3CR1表达,检测PTX对原代培养小胶质细胞的影响。
PTX减小了卒中后的梗死面积,改善了由Longa评分评估的神经功能,并减少了梗死区域小胶质细胞的聚集和激活。此外,PTX显著降低了脂多糖刺激的小胶质细胞增殖、白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的释放以及CX3CR1的表达。
卒中时PTX治疗减少了梗死区域小胶质细胞的积聚和激活,从而产生更好的功能结局。PTX治疗的益处可能归因于促炎细胞因子如IL-1β和TNF-α的产生减少以及趋化因子CX3CR1的表达降低。