Depletion of microglia exacerbates postischemic inflammation and brain injury

Wei Na Jin, Samuel Xiang Yu Shi, Zhiguo Li, Minshu Li, Kristofer Wood, Rayna J Gonzales, Qiang Liu

Research output: Contribution to journalArticle

54 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2224-2236
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number6
DOIs
StatePublished - Jun 1 2017

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Microglia
Brain Injuries
Inflammation
Colony-Stimulating Factor Receptors
Brain Ischemia
Astrocytes
Macrophage Colony-Stimulating Factor
Ischemia
Neuroprotective Agents
Stroke
Brain Infarction
Transient Ischemic Attack
Reperfusion
Monocytes
Leukocytes
Cell Death
Lymphocytes

Keywords

  • Brain ischemia
  • Colony-stimulating factor 1 receptor
  • Microglia
  • Neuroprotection

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Depletion of microglia exacerbates postischemic inflammation and brain injury. / Jin, Wei Na; Shi, Samuel Xiang Yu; Li, Zhiguo; Li, Minshu; Wood, Kristofer; Gonzales, Rayna J; Liu, Qiang.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 37, No. 6, 01.06.2017, p. 2224-2236.

Research output: Contribution to journalArticle

Jin, Wei Na ; Shi, Samuel Xiang Yu ; Li, Zhiguo ; Li, Minshu ; Wood, Kristofer ; Gonzales, Rayna J ; Liu, Qiang. / Depletion of microglia exacerbates postischemic inflammation and brain injury. In: Journal of Cerebral Blood Flow and Metabolism. 2017 ; Vol. 37, No. 6. pp. 2224-2236.
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