miR-24 protects against ischemia-induced brain damage in rats via regulating microglia polarization by targeting...

Microglia and macrophages play important roles in ischemic brain injury. Changes in their M1/M2 polarization phenotypes significantly impact disease progression. The M2 microglia/macrophages are anti-inflammatory and have a protective effect against ischemic injury. The microRNA 24 (miR-24) promotes M2 macrophage polarization and suppresses inflammation. We tested the hypothesis that miR-24 is protective in ischemic brain injury by regulating microglia polarization. We treated rats with miR-24 inhibitor or mimic and subsequently subjected the rats to middle cerebral artery occlusion (MCAO) to induce ischemic brain injury. Neurological deficit and infarct volume were analyzed. Microglia and macrophages were assessed by fluorescence-activated cell sorting. Microglia polarization was determined by genes specific for M1 and M2 both in vivo and in BV-2 cells. The effect of miR-24 target Clcn3 on microglia polarization was examined. We found that miR-24 inhibition aggravated MCAO induced damage, while miR-24 overexpression alleviated brain injury by suppressing microglia/macrophage infiltration. miR-24 suppressed M1 and promoted M2 microglia polarization both in vivo and in vitro. Finally, we showed that miR-24 targeted Clcn3 to regulate microglia polarization. Our study indicates that miR-24 plays a neuroprotective role by promoting anti-proinflammatory microglia polarization during ischemic brain injury.