Data_Sheet_3_Differential effects on TDP-43, piezo-2, tight-junction proteins in various brain regions following repetitive low-intensity blast overpressure.CSV

IntroductionMild traumatic brain injury (mTBI) caused by repetitive low-intensity blast overpressure (relBOP) in military personnel exposed to breaching and heavy weapons is often unrecognized and is understudied. Exposure to relBOP poses the risk of developing abnormal behavioral and psychological changes such as altered cognitive function, anxiety, and depression, all of which can severely compromise the quality of the life of the affected individual. Due to the structural and anatomical heterogeneity of the brain, understanding the potentially varied effects of relBOP in different regions of the brain could lend insights into the risks from exposures.
MethodsIn this study, using a rodent model of relBOP and western blotting for protein expression we showed the differential expression of various neuropathological proteins like TDP-43, tight junction proteins (claudin-5, occludin, and glial fibrillary acidic protein (GFAP)) and a mechanosensitive protein (piezo-2) in different regions of the brain at different intensities and frequency of blast.
ResultsOur key results include (i) significant increase in claudin-5 after 1x blast of 6.5 psi in all three regions and no definitive pattern with higher number of blasts, (ii) significant increase in piezo-2 at 1x followed by significant decrease after multiple blasts in the cortex, (iii) significant increase in piezo-2 with increasing number of blasts in frontal cortex and mixed pattern of expression in hippocampus and (iv) mixed pattern of TDP-3 and GFAP expression in all the regions of brain.
DiscussionThese results suggest that there are not definitive patterns of changes in these marker proteins with increase in intensity and/or frequency of blast exposure in any particular region; the changes in expression of these proteins are different among the regions. We also found that the orientation of blast exposure (e.g. front vs. side exposure) affects the altered expression of these proteins.

引言
轻度创伤性脑损伤（mild traumatic brain injury, mTBI）由暴露于破门装备与重型武器的军事人员所承受的重复性低强度爆炸超压（repetitive low-intensity blast overpressure, relBOP）引发，该病症常未被及时识别且研究程度不足。暴露于重复性低强度爆炸超压会使个体出现异常行为与心理改变，例如认知功能受损、焦虑及抑郁，上述症状均会严重降低患者的生活质量。由于大脑存在结构与解剖异质性，明确重复性低强度爆炸超压在不同脑区的潜在差异化影响，可为该暴露相关风险的研究提供新的视角。

研究方法
本研究采用重复性低强度爆炸超压啮齿动物模型，借助蛋白质印迹法（western blotting）检测蛋白质表达水平，结果显示在不同强度与频次的爆炸暴露下，大脑不同区域的多种神经病理相关蛋白表达存在差异，这些蛋白包括TDP-43、紧密连接蛋白（tight junction proteins）（Claudin-5、Occludin及胶质纤维酸性蛋白（glial fibrillary acidic protein, GFAP））以及机械敏感蛋白（piezo-2）。

研究结果
本研究的核心结果包括：
(i) 1次6.5磅每平方英寸的爆炸暴露后，三个脑区的Claudin-5表达均显著升高，但随着爆炸频次增加未呈现明确的变化模式；
(ii) 大脑皮层中Piezo2的表达在1次爆炸暴露后显著升高，而在多次爆炸暴露后显著降低；
(iii) 前额叶皮层中Piezo2的表达随爆炸频次增加而显著升高，而海马体中该蛋白的表达呈现混合变化模式；
(iv) 所有脑区中TDP-3与GFAP的表达均呈现混合变化模式。

讨论
上述结果表明，在任意特定脑区中，上述标记蛋白的表达变化均未随爆炸暴露强度和/或频次的增加呈现明确的变化模式；不同脑区的蛋白表达变化存在差异。本研究同时发现，爆炸暴露的朝向（例如正面朝向与侧面朝向）会影响上述蛋白的表达改变。