Depletion of microglia exacerbates postischemic inflammation and brain injury
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- Wei-Na Jin
- Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China
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- Samuel Xiang-Yu Shi
- Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA
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- Zhiguo Li
- Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China
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- Minshu Li
- Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China
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- Kristofer Wood
- Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA
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- Rayna J Gonzales
- Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, USA
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- Qiang Liu
- Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China
抄録
<jats:p> 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. </jats:p>
収録刊行物
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- Journal of Cerebral Blood Flow & Metabolism
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Journal of Cerebral Blood Flow & Metabolism 37 (6), 2224-2236, 2017-02-20
SAGE Publications