Affiliation:
1. Xijing Hospital of Air Force Military Medical University
2. Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine
Abstract
Abstract
Microglia play a central role in maintenance of brain homeostasis. Microglial polarization plays an important role in the recovery of homeostasis after acute ischemic stroke (AIS). DCPIB, as a blocker of volume-regulated ion channel plays an important role in maintaining intracellular homeostasis. But the relationship between DCPIB and microglial M1/M2 polarization is currently unclear. This study is to investigate the relationship between DCPIB and microglial M1/M2 polarization after AIS. C57BL/6 mice were subjected to transient middle cerebral artery occlusion (tMCAO). DCPIB was given within 5 min after reperfusion. Behavior assessments were conducted at 1, 3, and 7 days after tMCAO. Pathological injuries were evaluated by TTC, HE and Nissl staining and immunofluorescence co-staining (IFC). The phenotypic variations of microglia were examined by IFC. The levels of inflammatory cytokines were analyzed by RT-PCR and ELISA. In mice tMCAO model, DCPIB remarkably reduced mortality, pathological injury and improved behavioral performance and alleviated. DCPIB significantly inhibited inflammatory response, promoted the conversion of M1 microglia to the M2 via MAPK pathway and protected neurons from microglia-mediated inflammatory response. In addition, it was found that DCPIB inhibited oxidative stress after AIS. In conclusions, DCPIB attenuates ischemia-reperfusion injury via regulating microglial M1/M2 polarization and oxidative stress.
Publisher
Research Square Platform LLC