Depletion of microglia exacerbates postischemic inflammation and brain injury

WN Jin, SXY Shi, Z Li, M Li, K Wood… - Journal of Cerebral …, 2017 - journals.sagepub.com
WN Jin, SXY Shi, Z Li, M Li, K Wood, RJ Gonzales, Q Liu
Journal of Cerebral Blood Flow & Metabolism, 2017journals.sagepub.com
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 …
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.
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