Caruso James P, Susick Laura L, Charlton Jennifer L, Henson Emily L, Conti Alana C
John D. Dingell VA Medical Center and Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Brain Circ. 2016 Oct-Dec;2(4):183-188. doi: 10.4103/2394-8108.195284. Epub 2016 Dec 6.
Civilians and military personnel develop a range of physical and psychosocial impairments following traumatic brain injury (TBI), including alcohol abuse. As a consequence, increased rates of alcohol misuse magnify TBI-induced pathologies and impede rehabilitation efforts. Therefore, a developed understanding of the mechanisms that foster susceptibility of the injured brain to alcohol sensitivity and the response of the injured brain to alcohol is imperative for the treatment of TBI patients. Alcohol sensitivity has been demonstrated to be increased following experimental TBI and, in additional studies, regulated by presynaptic vesicle release mechanisms, including synapsin phosphorylation.
Mice were exposed to controlled midline impact of the intact skull and assessed for cortical, hippocampal, and striatal expression of phosphorylated synapsin I and II in response to high-dose ethanol exposure administered 14 days following injury, a time point at which injured mice demonstrate increased sedation after ethanol exposure.
Immunoblot quantitation revealed that TBI alone, compared to sham controls, significantly increased phosphorylated synapsin I and II protein expression in the striatum. In sham controls, ethanol administration significantly increased phosphorylated synapsin I and II protein expression compared to saline-treated sham controls; however, no significant increase in ethanol-induced phosphorylated synapsin I and II protein expression was observed in the striatum of injured mice compared to saline-treated TBI controls. A similar expression pattern was observed in the cortex although restricted to increases in phosphorylated synapsin II.
These data show that increased phosphorylated synapsin expression in the injured striatum may reflect a compensatory neuroplastic response to TBI which is proposed to occur as a result of a compromised presynaptic response of the injured brain to high-dose ethanol. These results offer a mechanistic basis for the altered ethanol sensitivity observed following experimental TBI and contribute to our understanding of alcohol action in the injured brain.
平民和军事人员在创伤性脑损伤（TBI）后会出现一系列身体和心理社会损伤，包括酒精滥用。因此，酒精滥用率的增加会加剧TBI引发的病变并阻碍康复进程。所以，深入了解促使受伤大脑对酒精敏感的机制以及受伤大脑对酒精的反应，对于治疗TBI患者至关重要。实验性TBI后已证明酒精敏感性会增加，并且在其他研究中，其受突触前囊泡释放机制调节，包括突触结合蛋白磷酸化。
小鼠接受完整颅骨的控制性中线撞击，并在受伤后14天给予高剂量乙醇暴露，评估皮质、海马和纹状体中磷酸化突触结合蛋白I和II的表达，这是受伤小鼠在乙醇暴露后表现出镇静增强的时间点。
免疫印迹定量分析显示，与假手术对照组相比，单纯TBI显著增加了纹状体中磷酸化突触结合蛋白I和II的蛋白表达。在假手术对照组中，与生理盐水处理的假手术对照组相比，乙醇给药显著增加了磷酸化突触结合蛋白I和II的蛋白表达；然而，与生理盐水处理的TBI对照组相比，受伤小鼠纹状体中乙醇诱导的磷酸化突触结合蛋白I和II的蛋白表达没有显著增加。在皮质中观察到类似的表达模式，尽管仅限于磷酸化突触结合蛋白II的增加。
这些数据表明，受伤纹状体中磷酸化突触结合蛋白表达的增加可能反映了对TBI的一种代偿性神经可塑性反应，这种反应被认为是受伤大脑对高剂量乙醇的突触前反应受损所致。这些结果为实验性TBI后观察到的乙醇敏感性改变提供了一个机制基础，并有助于我们理解酒精在受伤大脑中的作用。
