Depletion of microglia exacerbates postischemic inflammation and brain injury.
Depletion of microglia exacerbates postischemic inflammation and brain injury.
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小胶质细胞的消耗加剧了缺血后炎症和脑损伤
DOI：
10.1177/0271678x17694185
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
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作者：
Jin WN;Shi SX;Li Z;Li M;Wood K;Gonzales RJ;Liu Q
脑缺血诱发小胶质细胞活化和存活依赖于通过集落刺激因子1受体（CSF 1 R）的信号传导。尽管小胶质细胞的耗竭与更糟糕的中风结局有关，但仍不清楚激活的小胶质细胞在多大程度上以及通过何种机制影响脑缺血诱导的炎症和损伤。使用短暂局灶性脑缺血和再灌注的小鼠模型，我们证明了通过施用CSF 1 R/c-Kit双重抑制剂PLX 3397消耗小胶质细胞会加剧神经缺陷和脑梗死。在脑缺血期间，小胶质细胞的耗竭增加了炎症介质的产生、白细胞浸润和细胞死亡。值得注意的是，小胶质细胞耗竭诱导的卒中严重程度加重并不仅仅取决于淋巴细胞和单核细胞。重要的是，小胶质细胞的耗竭显著增加了脑缺血后星形胶质细胞产生的炎症介质。体外研究表明，小胶质细胞限制缺血诱导的星形胶质细胞反应，并提供神经保护作用。我们的研究结果表明，小胶质细胞的神经保护作用，可能会导致，部分是由于其抑制作用，对星形胶质细胞的反应缺血后。
Brain ischemia elicits microglial activation and microglia survival depend on signaling through colony-stimulating factor 1 receptor (CSF1R). Although depletion of microglia has been linked to worse stroke outcomes, it remains unclear to what extent and by what mechanisms activated microglia influence ischemia-induced inflammation and injury in the brain. Using a mouse model of transient focal cerebral ischemia and reperfusion, we demonstrated that depletion of microglia via administration of the dual CSF1R/c-Kit inhibitor PLX3397 exacerbates neurodeficits and brain infarction. Depletion of microglia augmented the production of inflammatory mediators, leukocyte infiltration, and cell death during brain ischemia. Of note, microglial depletion-induced exacerbation of stroke severity did not solely depend on lymphocytes and monocytes. Importantly, depletion of microglia dramatically augmented the production of inflammatory mediators by astrocytes after brain ischemia. In vitro studies reveal that microglia restricted ischemia-induced astrocyte response and provided neuroprotective effects. Our findings suggest that neuroprotective effects of microglia may result, in part, from its inhibitory action on astrocyte response after ischemia.