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爆炸暴露的长期影响:使用先进爆炸模拟器的大鼠功能研究。

Long-Term Effects of Blast Exposure: A Functional Study in Rats Using an Advanced Blast Simulator.

机构信息

Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland.

出版信息

J Neurotrauma. 2020 Feb 15;37(4):647-655. doi: 10.1089/neu.2019.6591. Epub 2019 Nov 13.

Abstract

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.

摘要

对爆炸受害者的偶然观察表明,在生命的后期可能会出现显著的神经病理学和神经行为缺陷。为了在临床前模拟这种现象,我们使用先进的爆炸模拟器检查了大鼠在单次和紧密耦合的重复爆炸暴露后长达 1 年的神经行为变化。使用 Morris 水迷宫测试空间学习和记忆、新物体识别测试短期记忆、开阔场探索活动作为焦虑/抑郁测试、旋转杆测试前庭运动功能以及旋转棒平衡测试运动协调,在急性、亚急性和慢性时间点监测神经行为变化。单次和重复爆炸在急性和慢性时间点都导致了明显的功能缺陷。在大多数功能测试中,重复爆炸暴露的大鼠比单次爆炸暴露的大鼠表现更差。有趣的是,爆炸后几个功能缺陷在 6 个月及以后最为明显。在爆炸暴露后早期出现明显的神经运动障碍,并且随着重复暴露严重程度增加。新物体识别测试在爆炸后 6 和 12 个月时显示出短期记忆缺陷。水迷宫测试显示在爆炸后急性和慢性阶段存在损伤。在爆炸暴露的大鼠中,最显著的变化是在开阔场探索测试的中心时间和边缘时间遗产中,在 6、9 和 12 个月后观察到。值得注意的是,这两个结果指标在急性时几乎没有改变,在亚急性阶段恢复,在爆炸暴露后的慢性阶段明显受到影响,可能表明慢性焦虑和抑郁样行为的发展。

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