Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
PLoS One. 2012;7(4):e33798. doi: 10.1371/journal.pone.0033798. Epub 2012 Apr 6.
Explosive blast results in multiple organ injury and polytrauma, the intensity of which varies with the nature of the exposure, orientation, environment and individual resilience. Blast overpressure alone may not precisely indicate the level of body or brain injury after blast exposure. Assessment of the extent of body injury after blast exposure is important, since polytrauma and systemic factors significantly contribute to blast-induced traumatic brain injury. We evaluated the activity of plasma enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatine kinase (CK) at different time points after blast exposure using a mouse model of single and repeated blast exposures to assess the severity of injury. Our data show that activities of all the enzymes in the plasma were significantly increased as early as 1 h after blast exposure. The elevated enzyme activity remained up to 6 h in an overpressure dose-dependent manner and returned close to normal levels at 24 h. Head-only blast exposure with body protection showed no increase in the enzyme activities suggesting that brain injury alone does not contribute to the systemic increase. In contrast to plasma increase, AST, ALT and LDH activity in the liver and CK in the skeletal muscle showed drastic decrease at 6 h after blast exposures. Histopathology showed mild necrosis at 6 h and severe necrosis at 24 h after blast exposures in liver and no changes in the skeletal muscle suggesting that the enzyme release from the tissue to plasma is probably triggered by transient cell membrane disruption from shockwave and not due to necrosis. Overpressure dependent transient release of tissue enzymes and elevation in the plasma after blast exposure suggest that elevated enzyme activities in the blood can be potentially used as a biological dosimeter to assess the severity of blast injury.
爆炸冲击波会导致多器官损伤和多发伤,其严重程度因暴露的性质、方向、环境和个体弹性而异。爆炸超压本身并不能准确表明爆炸暴露后身体或大脑的损伤程度。评估爆炸暴露后身体损伤的程度很重要,因为多发伤和全身因素会显著导致爆炸引起的创伤性脑损伤。我们使用单次和重复爆炸暴露的小鼠模型评估了不同时间点血浆酶(包括天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)和肌酸激酶(CK))的活性,以评估损伤的严重程度。我们的数据显示,早在爆炸暴露后 1 小时,所有血浆酶的活性都显著增加。在超压剂量依赖性的情况下,升高的酶活性持续到 6 小时,并在 24 小时内接近正常水平。有身体保护的头部单独爆炸暴露没有增加酶活性,这表明单独的脑损伤不会导致全身增加。与血浆增加相反,肝脏中的 AST、ALT 和 LDH 活性以及骨骼肌中的 CK 在爆炸暴露后 6 小时急剧下降。组织病理学显示,在爆炸暴露后 6 小时出现轻度坏死,24 小时出现严重坏死,骨骼肌无变化,这表明组织中酶的释放到血浆可能是由冲击波引起的瞬时细胞膜破裂触发的,而不是由于坏死。爆炸暴露后超压依赖性的组织酶短暂释放和血浆中酶活性升高提示,血液中升高的酶活性可以作为生物剂量计,用于评估爆炸损伤的严重程度。