Distinct patterns of expression of traumatic brain injury biomarkers after blast exposure: Role of compromised cell membrane integrity

Distinct patterns of expression of traumatic brain injury biomarkers after blast exposure: Role of compromised cell membrane integrity
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DOI:
10.1016/j.neulet.2013.07.047
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发表时间:
2013-09-27
影响因子:
2.5
通讯作者:
Nambiar, Madhusoodana P.
Nambiar, Madhusoodana P.
中科院分区:
医学4区
文献类型:
--
作者:
Arun, Peethambaran;Abu-Taleb, Rania;Nambiar, Madhusoodana P.

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胶质细胞酸性蛋白(GFAP),一种富含星形胶质细胞的蛋白质,和Tau,一种富含神经元微管的蛋白质,正被广泛研究作为脑损伤的生物标志物,并且已经报道了脑和血液中持续的严重程度依赖性增加。对这些蛋白在冲击波暴露后的急性变化的研究有限。使用小鼠模型的紧密耦合重复冲击波曝光,我们已经评估了急性变化的GFAP和总Tau蛋白的蛋白质印迹法的水平。脑组织GFAP和Tau蛋白水平在6 h时显著降低,24 h时显著升高。血浆样品显示在此时间范围内相似的初始降低和随后的升高。这种双相模式表明,这些蛋白质可能在反复爆炸暴露后立即从血浆中吸收或隔离。肝脏和脾脏组织中GFAP和Tau蛋白的水平显着增加,在6和24小时后爆炸曝光,而肝脏的半定量RT-PCR分析显示GFAP或Tau mRNA的水平没有显着变化。这些结果表明,冲击波暴露导致多个器官中细胞膜完整性的短暂变化,导致蛋白质从组织异常迁移到血浆,反之亦然。这种细胞膜通透性的瞬时变化和随后的分子双向运动可能有助于冲击波暴露后TBI和多发性创伤的病理生理学。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Glial fibrillary acidic protein (GFAP), a protein enriched in astrocytes, and Tau, a protein abundant in neuronal microtubules, are being widely studied as biomarkers of brain injury, and persistent severity-dependent increases in brain and blood have been reported. Studies on the acute changes of these proteins after blast exposure are limited. Using a mouse model of closely-coupled repeated blast exposures, we have evaluated acute changes in the levels of GFAP and total Tau by Western blotting. Brain levels of GFAP and Tau proteins decreased significantly at 6 h and increased considerably at 24 h after repeated blast exposures. Plasma samples showed a similar initial decrease and later increase over this timeframe. This biphasic pattern points to possible absorption or sequestration of these proteins from plasma immediately after repeated blast exposures. Liver and spleen tissue showed significant increases in the levels of GFAP and Tau protein at 6 and 24 h post-blast exposures whereas semi-quantitative RT-PCR analysis of liver showed no significant changes in the levels of GFAP or Tau mRNAs. These results suggest that blast exposure causes transient changes in cell membrane integrity in multiple organs leading to abnormal migration of proteins from the tissues to the plasma and vice versa. This transient changes in cell membrane permeability and subsequent bidirectional movement of molecules may contribute to the pathophysiology of TBI and polytrauma after blast exposure. (C) 2013 Elsevier Ireland Ltd. All rights reserved.