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Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury
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نویسنده
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dohi k. ,ohtaki h. ,nakamachi t. ,yofu s. ,satoh k. ,miyamoto k. ,song d. ,tsunawaki s. ,shioda s. ,aruga t.
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منبع
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journal of neuroinflammation - 2010 - دوره : 7 - شماره : 0
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چکیده
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Background: we hypothesized that gp91phox(nox2),a subunit of nadph oxidase,generates superoxide anion (o2 -) and has a major causative role in traumatic brain injury (tbi). to evaluate the functional role of gp91phoxand reactive oxygen species (ros) on tbi,we carried out controlled cortical impact in gp91phoxknockout mice (gp91phox-/-). we also used a microglial cell line to determine the activated cell phenotype that contributes to gp91phoxgeneration.methods: unilateral tbi was induced in gp91phox-/-and wild-type (wt) mice (c57/b6j) (25-30 g). the expression and roles of gp91phoxafter tbi were investigated using immunoblotting and staining techniques. levels of o2 -and peroxynitrite were determined in situ in the mouse brain. the activated phenotype in microglia that expressed gp91phoxwas determined in a microglial cell line,bv-2,in the presence of ifnγ or il-4.results: gp91phoxexpression increased mainly in amoeboid-shaped microglial cells of the ipsilateral hemisphere of wt mice after tbi. the contusion area,number of tunel-positive cells,and amount of o2 -and peroxynitrite metabolites produced were less in gp91phox-/-mice than in wt. in the presence of ifnγ,bv-2 cells had increased inducible nitric oxide synthase and nitric oxide levels,consistent with a classical activated phenotype,and drastically increased expression of gp91phox.conclusions: classical activated microglia promote ros formation through gp91phoxand have an important role in brain damage following tbi. modulating gp91phoxand gp91phox-derived ros may provide a new therapeutic strategy in combating post-traumatic brain injury. © 2010 dohi et al; licensee biomed central ltd.
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آدرس
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department of emergency and critical care medicine,showa university school of medicine,shinagawa-ku,tokyo 142-8555, Japan, department of anatomy,showa university school of medicine,shinagawa-ku,tokyo 142-8555, Japan, department of anatomy,showa university school of medicine,shinagawa-ku,tokyo 142-8555, Japan, department of anatomy,showa university school of medicine,shinagawa-ku,tokyo 142-8555, Japan, department of anatomy,showa university school of medicine,shinagawa-ku,tokyo 142-8555, Japan, department of emergency and critical care medicine,showa university school of medicine,shinagawa-ku,tokyo 142-8555, Japan, department of anatomy,showa university school of medicine,shinagawa-ku,tokyo 142-8555, Japan, department of infectious diseases,national research institute for child health and development,setagaya-ku,tokyo,157-8535, Japan, department of anatomy,showa university school of medicine,shinagawa-ku,tokyo 142-8555, Japan, department of emergency and critical care medicine,showa university school of medicine,shinagawa-ku,tokyo 142-8555, Japan
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Authors
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