Depletion of microglia exacerbates postischemic inflammation and brain injury. Issue 6 (June 2017)

• Record Type: Journal Article
• Authors: Jin, Wei-Na; Shi, Samuel Xiang-Yu; Li, Zhiguo; Li, Minshu; Wood, Kristofer; Gonzales, Rayna J; Liu, Qiang
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 37:Issue 6(2017)
• Page Start: 2224
• Page End: 2236
• Publication Date: 2017-06
• Subjects: Microglia -- brain ischemia -- colony-stimulating factor 1 receptor -- neuroprotection; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X17694185
• Languages: English
• ISSNs: 0271-678X

Abstract

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.