Microglia/Macrophage Polarization Dynamics Reveal Novel Mechanism of Injury Expansion After Focal Cerebral Ischemia

• DOI: 10.1161/strokeaha.112.659656
• Publication Date: 2012-08-29T05:22:05Z
• Authors: Xiaoming Hu; Peiying Li; Yanling Guo; Haiying Wang; Rehana K. Leak; Songela Chen; Yanqin Gao; Jun Chen
• Keywords: Macrophage polarization

Background and Purpose— Mononuclear phagocytes are highly plastic cells that assume diverse phenotypes in response to microenvironmental signals. The phenotype-specific roles of microglia/macrophages ischemic brain injury poorly understood. A comprehensive characterization microglia/macrophage polarization after ischemia may advance our knowledge poststroke damage/recovery. Methods— Focal transient cerebral was induced mice for 60 minutes; animals were euthanized at 1 14 days reperfusion. Reverse-transcriptase polymerase chain reaction immunohistochemical staining M1 M2 markers performed characterize phenotypic changes cells, including microglia infiltrating macrophages. In vitro experiments using a transwell system, conditioned medium transfer or coculture system allowing cell-to-cell contacts used further elucidate the effect neuronal on and, conversely, phenotype fate neurons. Results— Local newly recruited macrophages early stages stroke but gradually transformed into peri-infarct regions. revealed neurons prime microglial toward phenotype. M1-polarized M1-conditioned media exacerbated oxygen glucose deprivation–induced death. contrast, maintaining protected against deprivation. Conclusions— Our results suggest respond dynamically injury, experiencing an “healthy” phenotype, followed by transition “sick” These dual opposing therapies should be shifted from simply suppressing adjusting balance between beneficial detrimental responses.