TSPO ligand Ro5-4864 modulates microglia/macrophages polarization after subarachnoid hemorrhage in mice

摘要

Brain injury after subarachnoid hemorrhage (SAH) is closely related to microglia/macrophages-induced neuroinflammation. Translocator protein (TSPO) is a hall marker of activated microglia/macrophages, and the TSPO ligands have been proved to be beneficial for controlling neuroinflammation. Ro5-4864, one of the TSPO ligands, has been reported to be able to regulate inflammation in neurological diseases. Here, we investigated the effects of Ro5-4864 on microglia/macrophages polarization in a SAH mice model, which was induced by endovascular perforation. Ro5-4864 was administered intraperitoneally dissolved in DMSO-saline. Post-SAH assessments included neurological tests, SAH grade, western blotting, ELISA assay and immunohistochemistry. The results showed that brain injury was accompanied by the accumulation of TNF-alpha and IL-1 beta, as well as the increase of iNOS protein levels. Finally, we found that Ro5-4864 improved neurological function, increased the expression of anti-inflammatory factors, and influenced phenotypes of M2 microglia/macrophages after SAH. Together, these data reveal a protective role of TSPO ligand Ro5-4864 in inflammatory processes of SAH as well as a potential alternative for SAH treatment.