Long-Term Effects of Blast Exposure: A Functional Study in Rats Using an Advanced Blast Simulator
Long-Term Effects of Blast Exposure: A Functional Study in Rats Using an Advanced Blast Simulator
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DOI：
10.1089/neu.2019.6591
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发表时间：
2019-11-13
影响因子：
4.2
通讯作者：
Long, Joseph B.
中科院分区：
文献类型：
--
作者：
Arun, Peethambaran;Wilder, Donna M.;Long, Joseph B.
对爆炸受害者的轶事观察表明，在生命的后期阶段可能会出现重大的神经病理学和神经行为缺陷。为了对这种现象进行临床前建模，我们使用先进的冲击波模拟器研究了暴露于单次和紧耦合重复冲击波后长达1年的大鼠神经行为变化。在急性、亚急性和慢性时间点，使用空间学习和记忆的Morris水迷宫测试、短期记忆的新物体识别测试、焦虑/抑郁测试的旷场探索活动、前庭功能的旋转杆测试和运动协调的旋转杆平衡测试监测神经行为变化。单次和重复原始细胞在急性和慢性时间点均导致显著的功能缺陷。在大多数功能测试中，暴露于重复冲击波的大鼠比暴露于单次冲击波的大鼠表现更差。有趣的是，爆炸后的几个功能缺陷在6个月及以后最明显。在爆炸暴露后的早期阶段发生了显着的神经运动障碍，并随着重复暴露的严重程度增加。新的物体识别测试显示爆炸后6个月和12个月的短期记忆缺陷。水迷宫试验显示，在急性和慢性阶段的损伤后，冲击波暴露。爆炸暴露大鼠中最实质性的变化是在爆炸后6、9和12个月的旷场探索试验中观察到中心时间和边缘时间遗产。值得注意的是，这两个结果的措施是最低限度地改变急性，恢复在亚急性阶段，并在爆炸后的慢性阶段受到显着影响，并可能涉及慢性焦虑和抑郁样行为的发展。
Anecdotal observations of blast victims indicate that significant neuropathological and neurobehavioral defects may develop at later stages of life. To pre-clinically model this phenomenon, we have examined neurobehavioral changes in rats up to 1 year after exposure to single and tightly coupled repeated blasts using an advanced blast simulator. Neurobehavioral changes were monitored at acute, sub-acute, and chronic time-points using Morris water maze test of spatial learning and memory, novel object recognition test of short-term memory, open field exploratory activity as a test of anxiety/depression, a rotating pole test for vestibulomotor function, and a rotarod balance test for motor coordination. Single and repeated blasts resulted in significant functional deficits at both acute and chronic time-points. In most functional tests, rats exposed to repeated blasts performed more poorly than rats exposed to single blast. Interestingly, several functional deficits post-blast were most pronounced at 6 months and beyond. Significant neuromotor impairments occurred at early stages after blast exposure and the severity increased with repeated exposures. The novel object recognition testing revealed short-term memory deficits at 6 and 12 months post-blast. The water maze test revealed impairments at acute and chronic stages after blast exposure. The most substantial changes in the blast-exposed rats were observed with the center time and margin time legacies in the open field exploration test at 6, 9, and 12 months post-blast. Notably, these two outcome measures were minimally altered acutely, recovered during sub-acute stages, and were markedly affected during the chronic stages after blast exposures and may implicate development of chronic anxiety and depressive-like behaviors.