CLASS A SCAVENGER RECEPTOR PROMOTES CEREBRAL ISCHEMIC INJURY BY PIVOTING MICROGLIA/MACROPHAGE POLARIZATION

Class A scavenger receptor (SR-A) is primarily expressed in microglia/macrophages and plays an important role in immune responses. However, whether SR-A can influence microglia/macrophage polarization in cerebral ischemic injury is not known. To this end we monitored the phenotypic alteration of microglia/macrophages in an animal model of cerebral ischemia injury. SR-A was up-regulated in mouse brains 24 h after permanent occlusion of middle cerebral artery (MCAO). SR-A-deficient mice displayed reduced infarct size and improved neurological function compared with wild-type mice littermate controls. Furthermore, a decrease in inflammatory F4/80(+)CD11b(+) CD45(high)CD11c(+) microglia/macrophages and attenuated nuclear factor-kappaB (NF-kappa B) activation was found in ischemic brains in the SR-A null mice. This was accompanied by alleviation of classically activated M1 macrophage markers and preservation of alternatively activated M2 macrophage markers. These data suggest that SR-A contributes to cerebral ischemic injury by pivoting the phenotype of microglia/macrophages to a skewed M1 polarization. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.