1 Cell Biology Graduate Program, Department of Neuroscience and Cell Biology, Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas.
2 The Moody Project for Translational Traumatic Brain Injury Research, Charles R. Allen Research Laboratories, Department of Anesthesiology, Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas.
J Neurotrauma. 2018 Jan 15;35(2):375-392. doi: 10.1089/neu.2017.5256. Epub 2017 Dec 20.
To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry [LDF]), and mean arterial blood pressure (MAP) cerebral vascular resistance were measured for 2 h post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. Neuronal injury was assessed (Fluoro-Jade C [FJC]) 24 and 48 h post-bTBI. Neurological outcomes (beam balance and walking tests) and working memory (Morris water maze [MWM]) were assessed 2 weeks post-bTBI. Because impact TBI (i.e., non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function in part because of the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO), the effects of the administration of the ONOO scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for 2 h post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and in the numbers of FJC-positive cells in the brain, and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend toward increased cerebral perfusion, suggesting that ONOO may contribute to blast-induced cerebral vascular dysfunction.
为了确定轻度爆炸诱导性创伤性脑损伤（bTBI）的影响，几组大鼠在压缩空气驱动的激波管中接受爆炸伤或假伤。在 bTBI 后 2 小时内，通过激光多普勒血流计（LDF）测量 bTBI 对相对脑灌注（laser Doppler flowmetry [LDF]）和平均动脉血压（MAP）脑血管阻力的影响。在 bTBI 后 30 和 60 分钟，离体测量大脑中动脉（MCA）段对血管内压低的扩张反应。在 bTBI 后 24 和 48 小时评估神经元损伤（Fluoro-Jade C [FJC]）。在 bTBI 后 2 周评估神经功能结局（横梁平衡和行走测试）和工作记忆（Morris 水迷宫 [MWM]）。由于冲击性创伤性脑损伤（即非爆炸性创伤性脑损伤）通常与脑灌注减少和脑血管功能受损有关，部分原因是活性氧和氮物种（如过氧亚硝酸盐（ONOO））的产生，因此测量了 ONOO 清除剂 penicillamine 甲酯（PenME）在 bTBI 后 2 小时内对脑灌注和脑血管阻力的影响。轻度 bTBI 导致相对脑灌注减少和 MCA 对血管内压低的扩张反应减弱，脑血管阻力增加，脑中 FJC 阳性细胞数量增加，工作记忆明显受损。PenME 给药导致脑血管阻力显著降低，脑灌注有增加趋势，提示 ONOO 可能导致爆炸诱导的脑血管功能障碍。
