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Studies On Class A Scavenger Receptor-mediated Cerebral Ischemia Injury

Posted on:2013-04-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y M XuFull Text:PDF
GTID:1224330374992707Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
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.
Keywords/Search Tags:SR-A-deficient mice, microglia/macrophages subsets, stroke, inflammation, chemokines
PDF Full Text Request
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