critical role of nadph oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury关键作用的nadph氧化酶在神经元氧化损伤和创伤性脑损伤后小胶质细胞的激活.pdfVIP

Critical Role of NADPH Oxidase in Neuronal Oxidative Damage and Microglia Activation following Traumatic Brain Injury 1. 2. 1 1 1 1 Quan-Guang Zhang , Melissa D. Laird , Dong Han , Khoi Nguyen , Erin Scott , Yan Dong , 2 1 Krishnan M. Dhandapani , Darrell W. Brann * 1 Department of Neurology, Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, Georgia, United States of America, 2 Department of Neurosurgery, Georgia Health Sciences University, Augusta, Georgia, United States of America Abstract Background: 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 (O22), 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 O22 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 A