Department of Anesthesiology, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
Front Neurol. 2013 Dec 12;4:196. doi: 10.3389/fneur.2013.00196. eCollection 2013.
A significant proportion of the military personnel returning from Iraq and Afghanistan conflicts have suffered from both mild traumatic brain injury (mTBI) and post-traumatic stress disorder. The mechanisms are unknown. We used a rat model of repeated stress and mTBI to examine brain activity and behavioral function. Adult male Sprague-Dawley rats were divided into four groups: Naïve; 3 days repeated tail-shock stress; lateral fluid percussion mTBI; and repeated stress followed by mTBI (S-mTBI). Open field activity, sensorimotor responses, and acoustic startle responses (ASRs) were measured at various time points after mTBI. The protein expression of mitochondrial electron transport chain (ETC) complex subunits (CI-V) and pyruvate dehydrogenase (PDHE1α1) were determined in four brain regions at day 7-post mTBI. Compared to Naïves, repeated stress decreased horizontal activity; repeated stress and mTBI both decreased vertical activity; and the mTBI and S-mTBI groups were impaired in sensorimotor and ASRs. Repeated stress significantly increased CI, CII, and CIII protein levels in the prefrontal cortex (PFC), but decreased PDHE1α1 protein in the PFC and cerebellum, and decreased CIV protein in the hippocampus. The mTBI treatment decreased CV protein levels in the ipsilateral hippocampus. The S-mTBI treatment resulted in increased CII, CIII, CIV, and CV protein levels in the PFC, increased CI level in the cerebellum, and increased CIII and CV levels in the cerebral cortex, but decreased CI, CII, CIV, and PDHE1α1 protein levels in the hippocampus. Thus, repeated stress or mTBI alone differentially altered ETC expression in heterogeneous brain regions. Repeated stress followed by mTBI had synergistic effects on brain ETC expression, and resulted in more severe behavioral deficits. These results suggest that repeated stress could have contributed to the high incidence of long-term neurologic and neuropsychiatric morbidity in military personnel with or without mTBI.
相当比例的从伊拉克和阿富汗冲突中返回的军事人员患有轻度创伤性脑损伤（mTBI）和创伤后应激障碍。其机制尚不清楚。我们使用大鼠重复应激和 mTBI 模型来检查大脑活动和行为功能。成年雄性 Sprague-Dawley 大鼠分为四组：天真组；3 天重复尾部冲击应激组；侧方液压冲击 mTBI 组；重复应激后 mTBI 组（S-mTBI 组）。mTBI 后不同时间点测量旷场活动、感觉运动反应和听觉惊跳反应（ASR）。mTBI 后第 7 天，测定四个脑区线粒体电子传递链（ETC）复合物亚基（CI-V）和丙酮酸脱氢酶（PDHE1α1）的蛋白表达。与天真组相比，重复应激降低了水平活动；重复应激和 mTBI 均降低了垂直活动；mTBI 和 S-mTBI 组在感觉运动和 ASR 方面受损。重复应激显著增加了前额叶皮质（PFC）中的 CI、CII 和 CIII 蛋白水平，但降低了 PFC 和小脑的 PDHE1α1 蛋白水平，并降低了海马体中的 CIV 蛋白水平。mTBI 处理降低了同侧海马体中的 CV 蛋白水平。S-mTBI 处理导致 PFC 中的 CII、CIII、CIV 和 CV 蛋白水平增加，小脑中的 CI 水平增加，大脑皮质中的 CIII 和 CV 水平增加，但降低了海马体中的 CI、CII、CIV 和 PDHE1α1 蛋白水平。因此，单独重复应激或 mTBI 会导致不同脑区 ETC 表达的改变。重复应激后 mTBI 对脑 ETC 表达具有协同作用，并导致更严重的行为缺陷。这些结果表明，重复应激可能导致患有或不患有 mTBI 的军事人员长期神经和神经精神发病率较高。
