Heyburn Lanier, Dahal Shataakshi, Abutarboush Rania, Reed Eileen, Urioste Rodrigo, Batuure Andrew, Wilder Donna, Ahlers Stephen T, Long Joseph B, Sajja Venkatasivasai Sujith
Blast Induced Neurotrauma Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
The Geneva Foundation, Tacoma, WA, United States.
Front Neurol. 2023 Oct 9;14:1237647. doi: 10.3389/fneur.2023.1237647. eCollection 2023.
Mild 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.
In 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.
Our 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.
These 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.
在接触爆破和重型武器的军事人员中，由重复性低强度爆炸超压（relBOP）导致的轻度创伤性脑损伤（mTBI）常常未被识别且研究不足。暴露于relBOP会带来出现异常行为和心理变化的风险，如认知功能改变、焦虑和抑郁，所有这些都会严重损害受影响个体的生活质量。由于大脑结构和解剖的异质性，了解relBOP在大脑不同区域可能产生的不同影响有助于深入了解暴露带来的风险。
在本研究中，我们使用relBOP啮齿动物模型并通过蛋白质印迹法检测蛋白质表达，展示了在不同强度和频率的爆炸情况下，各种神经病理学蛋白质（如TDP - 43、紧密连接蛋白（claudin - 5、occludin和胶质纤维酸性蛋白（GFAP））以及一种机械敏感蛋白（piezo - 2））在大脑不同区域的差异表达。
我们的主要结果包括：（i）在所有三个区域，6.5磅力/平方英寸的单次爆炸后claudin - 5显著增加，而爆炸次数增加时无明确模式；（ii）在皮质中，单次爆炸后piezo - 2显著增加，多次爆炸后显著减少；（iii）在额叶皮质中，piezo - 2随着爆炸次数增加而显著增加，在海马体中表达模式混合；（iv）在大脑所有区域中，TDP - 3和GFAP的表达模式混合。
这些结果表明，随着爆炸暴露强度和/或频率的增加，这些标记蛋白在任何特定区域都没有明确的变化模式；这些蛋白的表达变化在不同区域有所不同。我们还发现爆炸暴露的方向（例如正面暴露与侧面暴露）会影响这些蛋白的表达改变。
