Translocator protein regulate polarization phenotype transformation of microglia after cerebral ischemia-reperfusion injury.

Abstract Microglia cells are activated after cerebral ischemia-reperfusion injury (CIRI), playing a dual role in aggravating the injury or promoting tissue repair by polarization. Translocator protein (TSPO) is a biomarker of neuroinflammation or microglia activation. Its expression is significantly increased while brain injury and neuroinflammation occur. However, the relationship between TSPO and microglia polarization in CIRI is still not clear. In the present study, the middle cerebral artery occlusion (MCAO) methods in rats were used to simulate CIRI. We found that the expressions of M1 markers (CD86, IL-1β, and TNF-α) and M2 markers (CD206, IL-10, and TGF-β) were significantly increased. Moreover, the injection of TSPO ligand, PK11195, inhibited the increase of M1 polarization markers but promoted the expressions of M2 polarization markers, which significantly reversed the neurological damage after MCAO in rats. In vitro studies showed that shRNA-mediated TSPO knock-down promoted M1 polarization but inhibited M2 polarization, accompanied by a significant decrease in cell viability. On the contrary, overexpression of TSPO inhibited M1 polarization, promoted M2 polarization, and significantly improved cell viability. In summary, TSPO plays a neuroprotective role in CIRI by inhibiting M1 polarization and promoting M2 polarization, which suggests that TSPO may have the potential to serve as a therapeutic target for stroke.