Critical Role of NADPH Oxidase in Neuronal Oxidative Damage and Microglia Activation following Traumatic Brain Injury
Laird, Melissa D
Scott, Erin L.
Dhandapani, Krishnan M.
Brann, Darrell W
MetadataShow full item record
AbstractBackground: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS) following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O2^-), and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI.
Methodology/Principal Findings: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O2â induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins b-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI.
Conclusions/Significance: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.
CitationPLoS One. 2012 Apr 2; 7(4):e34504
- Involvement of Nox2 and Nox4 NADPH oxidases in early brain injury after subarachnoid hemorrhage.
- Authors: Zhang L, Li Z, Feng D, Shen H, Tian X, Li H, Wang Z, Chen G
- Issue date: 2017 Mar
- NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice.
- Authors: Qiu LL, Ji MH, Zhang H, Yang JJ, Sun XR, Tang H, Wang J, Liu WX, Yang JJ
- Issue date: 2016 Jan
- NADPH oxidases in traumatic brain injury - Promising therapeutic targets?
- Authors: Ma MW, Wang J, Dhandapani KM, Wang R, Brann DW
- Issue date: 2018 Jun
- Novel mGluR5 positive allosteric modulator improves functional recovery, attenuates neurodegeneration, and alters microglial polarization after experimental traumatic brain injury.
- Authors: Loane DJ, Stoica BA, Tchantchou F, Kumar A, Barrett JP, Akintola T, Xue F, Conn PJ, Faden AI
- Issue date: 2014 Oct
- Prevention of traumatic brain injury-induced neuronal death by inhibition of NADPH oxidase activation.
- Authors: Choi BY, Jang BG, Kim JH, Lee BE, Sohn M, Song HK, Suh SW
- Issue date: 2012 Oct 24