Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.; Center for Military Psychiatry and Neurosciences, Blast Induced Neurotrauma Group, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA..
Exp Neurol. 2022 Mar;349:113938. doi: 10.1016/j.expneurol.2021.113938. Epub 2021 Dec 1.
Blast-induced neurotrauma (BINT) is not only a signature injury to soldiers in combat field and training facilities but may also a growing concern in civilian population due to recent increases in the use of improvised explosives by insurgent groups. Unlike moderate or severe BINT, repeated low-level blast (rLLB) is different in its etiology as well as pathology. Due to the constant use of heavy weaponry as part of combat readiness, rLLB usually occurs in service members undergoing training as part of combat readiness. rLLB does not display overt pathological symptoms; however, earlier studies report chronic neurocognitive changes such as altered mood, irritability, and aggressive behavior, all of which may be caused by subtle neuropathological manifestations. Current animal models of rLLB for investigation of neurobehavioral and neuropathological alterations have not been adequate and do not sufficiently represent rLLB conditions. Here, we developed a rat model of rLLB by applying controlled low-level blast pressures (<10 psi) repeated successively five times to mimic the pressures experienced by service members. Using this model, we assessed anxiety-like symptoms, motor coordination, and short-term memory as a function of time. We also examined levels of superoxide-producing enzyme NADPH oxidase, microglial activation, and reactive astrocytosis as factors likely contributing to these neurobehavioral changes. Animals exposed to rLLB displayed acute and chronic anxiety-like symptoms, motor and short-term memory impairments. These changes were paralleled by increased microglial activation and reactive astrocytosis. Conversely, animals exposed to a single low-level blast did not display significant changes. Collectively, this study demonstrates that, unlike a single low-level blast, rLLB exerts a cumulative impact on different brain regions and produces chronic neuropathological changes in so doing, may be responsible for neurobehavioral alterations.
爆炸所致神经创伤（BINT）不仅是战斗环境和训练设施中士兵的标志性损伤，由于叛乱团体最近增加使用简易爆炸装置，也可能成为平民群体日益关注的问题。与中度或重度 BINT 不同，反复低水平爆炸（rLLB）在病因和病理学上有所不同。由于作为战备的一部分经常使用重武器，rLLB 通常发生在进行战备训练的现役军人中。rLLB 没有明显的病理症状；然而，早期研究报告称慢性神经认知变化，如情绪改变、易怒和攻击性行为，所有这些都可能是由微妙的神经病理学表现引起的。目前用于研究神经行为和神经病理学改变的 rLLB 动物模型不够充分，不能充分代表 rLLB 情况。在这里，我们通过连续五次施加受控的低水平爆炸压力（<10 psi）来模拟现役军人所经历的压力，开发了一种 rLLB 的大鼠模型。使用该模型，我们评估了焦虑样症状、运动协调和短期记忆作为时间的函数。我们还检查了超氧化物产生酶 NADPH 氧化酶、小胶质细胞激活和反应性星形胶质细胞增生的水平，作为可能导致这些神经行为变化的因素。暴露于 rLLB 的动物表现出急性和慢性焦虑样症状、运动和短期记忆障碍。这些变化伴随着小胶质细胞激活和反应性星形胶质细胞增生的增加。相比之下，单次低水平爆炸暴露的动物没有显示出显著变化。总的来说，这项研究表明，与单次低水平爆炸不同，rLLB 对不同的大脑区域产生累积影响，并因此产生慢性神经病理学变化，可能是导致神经行为改变的原因。
