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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2010

Open Access 01-12-2010 | Research

Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury

Authors: Kenji Dohi, Hirokazu Ohtaki, Tomoya Nakamachi, Sachiko Yofu, Kazue Satoh, Kazuyuki Miyamoto, Dandan Song, Shohko Tsunawaki, Seiji Shioda, Tohru Aruga

Published in: Journal of Neuroinflammation | Issue 1/2010

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Abstract

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 gp91phox and reactive oxygen species (ROS) on TBI, we carried out controlled cortical impact in gp91phox knockout mice (gp91phox-/-). We also used a microglial cell line to determine the activated cell phenotype that contributes to gp91phox generation.

Methods

Unilateral TBI was induced in gp91phox-/- and wild-type (Wt) mice (C57/B6J) (25-30 g). The expression and roles of gp91phox after 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 gp91phox was determined in a microglial cell line, BV-2, in the presence of IFNγ or IL-4.

Results

Gp91phox expression 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 gp91phox and have an important role in brain damage following TBI. Modulating gp91phox and gp91phox -derived ROS may provide a new therapeutic strategy in combating post-traumatic brain injury.
Appendix
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Metadata
Title
Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury
Authors
Kenji Dohi
Hirokazu Ohtaki
Tomoya Nakamachi
Sachiko Yofu
Kazue Satoh
Kazuyuki Miyamoto
Dandan Song
Shohko Tsunawaki
Seiji Shioda
Tohru Aruga
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2010
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-7-41

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