Studies On Class A Scavenger Receptor-mediated Cerebral Ischemia Injury

The innate immune response is involved in the process of cerebral ischemia injury.Class A scavenger receptor (SR-A) is primarily expressed in microglia/macrophagesand plays an important role in immune responses. It has been reported that SR-A canpromote cerebral ischemic injury. However, whether SR-A can influencemicroglia/macrophage polarization in cerebral ischemic injury is not known yet. Weinvestigated the role of SR-A in cerebral ischemia injury by monitoring thephenotypic alteration in microglia/macrophages. SR-A expression was up-regulatedin mouse brains24hours after permanent occlusion of middle cerebral artery (MCAO)with no difference between classically activated M1and alternatively activated M2microglia/macrophages. SR-A-deficient mice displayed reduced infarct size and cellapoptosis and improved neurological function compared with wild type mice.Furthermore, a decrease in inflammatory F4/80+CD11b+CD45highCD11c+microglia/macrophages and attenuated nuclear factor-kappaB (NF-κB) activationwere found in ischemic brains in the SR-A null mice. This was accompanied byalleviation of classically activated M1macrophage markers and preservation ofalternatively activated M2macrophage markers. These data suggest that SR-Acontributes to cerebral ischemic injury by pivoting the phenotype ofmicroglia/macrophages to a skewed M1polarization.