Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury.
Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury.
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DOI：
10.1371/journal.pone.0034504
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Brann DW
中科院分区：
文献类型：
--
作者：
Zhang QG;Laird MD;Han D;Nguyen K;Scott E;Dong Y;Dhandapani KM;Brann DW
氧化应激在创伤性脑损伤的病理学中起重要作用。线粒体被认为是TBI后损伤性活性氧（ROS）的主要来源。然而，最近的研究表明，膜，通过酶NADPH氧化酶也可以产生超氧自由基（O2-），从而可能有助于TBI后的氧化应激。因此，本研究探讨了NADPH氧化酶在TBI中的潜在作用。结果表明，雄性小鼠脑损伤后，大脑皮层和海马CA 1区NADPH氧化酶活性迅速升高，在脑损伤后1h出现一个早期高峰，24-96 h出现一个次高峰。使用氧化氢乙啶和神经元标记物NeuN的原位定位显示，在TBI后1小时，神经元中发生了O2 −诱导。在用NADPH氧化酶抑制剂处理前或处理后，夹竹桃麻素显著抑制小胶质细胞活化和氧化应激损伤。夹竹桃麻素还减弱TBI对阿尔茨海默病蛋白β-淀粉样蛋白和淀粉样前体蛋白的诱导。最后，夹竹桃麻素的预处理和后处理也显示出诱导针对TBI的显著神经保护。此外，N 0X 2特异性抑制剂gp 91 ds-tat也显示出对TBI发挥神经保护作用。总的来说，该研究表明，NADPH氧化酶活性和超氧化物产生在TBI后的海马和皮质中表现出双相升高，这通过介导TBI后脑中的氧化应激损伤、小胶质细胞活化和AD蛋白诱导而显著促进TBI的病理学。
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. 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 O2 − 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 β-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. 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.
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影响因子：
9.3
作者：
Dohi K;Ohtaki H;Nakamachi T;Yofu S;Satoh K;Miyamoto K;Song D;Tsunawaki S;Shioda S;Aruga T
通讯作者：
Aruga T
影响因子：
4.7
作者：
Laird MD;Sukumari-Ramesh S;Swift AE;Meiler SE;Vender JR;Dhandapani KM
通讯作者：
Dhandapani KM
影响因子：
2.4
作者：
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通讯作者：
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影响因子：
3.8
作者：
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通讯作者：
Cox, Charles S., Jr.
影响因子：
3.5
作者：
Murotomi, Kazutoshi;Takagi, Norio;Tanonaka, Kouichi
通讯作者：
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