| Microglial cells contribute to endogenous brain defenses after acute neonatal focal stroke. | |
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MedLine Citation:
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PMID: 21900578 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Macrophages are viewed as amplifiers of ischemic brain injury, but the origin of injury-producing macrophages is poorly defined. The role of resident brain macrophages-microglial cells-in stroke remains controversial. To determine whether microglial cells exert injurious effects after neonatal focal stroke, we selectively depleted these cells with intracerebral injection of liposome-encapsulated clodronate before transient middle cerebral artery occlusion in postnatal day 7 rats. Phagocytosis of apoptotic neurons by activated microglia was poor in animals with unmanipulated microglia, and depletion of these cells did not increase the number of apoptotic neurons. Lack of microglia increased the brain levels of several cytokines and chemokines already elevated by ischemia-reperfusion, and also increased the severity and volume of injury, suggesting that microglial cells contribute to endogenous protection during the subacute injury phase. Then, to determine whether accumulation of reactive oxygen species in microglia adversely affects phagocytosis of dying neurons and contributes to injury, we delivered reduced glutathione (GSH) into microglia, again using liposomes. Remarkably, pharmacologically increased intracellular GSH concentrations in microglia induced superoxide accumulation in lipid rafts in these cells, further increased the brain levels of macrophage chemoattractants, and exacerbated injury. Together, these data show that microglia are part of the endogenous defense mechanisms and that, while antioxidants can protect the injured neonatal brain, high levels of reducing equivalents in activated microglia, GSH, trigger superoxide production, favor the reorganization of lipids, amplify local inflammation and exacerbate injury. |
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Authors:
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Joel V Faustino; Xia Wang; Cali E Johnson; Alexander Klibanov; Nikita Derugin; Michael F Wendland; Zinaida S Vexler |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 31 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-08 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 12992-3001 Citation Subset: IM |
Affiliation:
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Departments of Neurology and Radiology, University of California, San Francisco, San Francisco, California 94143-0663, Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, China, and Department of Medicine, University of Virginia, Charlottesville, Virginia 22908. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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