Behavioral and Histopathological Alterations Resulting from Mild Fluid Percussion Injury
Behavioral and Histopathological Alterations Resulting from Mild Fluid Percussion Injury
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DOI：
10.1089/neu.2012.2630
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发表时间：
2013-05-01
影响因子：
4.2
通讯作者：
Dash, Pramod K.
中科院分区：
文献类型：
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作者：
Hylin, Michael J.;Orsi, Sara A.;Dash, Pramod K.
大多数遭受创伤性脑损伤（TBI）的人都有轻度损伤（通常被称为脑震荡）。尽管大多数轻度TBI （mTBI）患者的头部CT扫描结果为阴性，但这些人仍可能患有神经认知和神经行为缺陷。为了加快临床前研究和开发治疗方法，有必要建立表征良好的mTBI动物模型，以反映人类患者的神经、神经认知和病理变化。在本研究中，我们检测了1.0和1.5大气压（atm）超压液体撞击损伤（FPI）引起的运动、认知和组织病理学变化。1.0和1.5 atm FPI损伤均引起急性神经功能的一过性抑制，但未造成明显的脑挫伤。1.0 atm FPI损伤的动物没有表现出明显的运动、前庭运动或学习和记忆缺陷。相反，1.5 atm损伤引起短暂性运动障碍，导致空间学习和短期记忆明显受损。此外，1.5 atm FPI可导致损伤部位脑灌注明显减少，并持续数小时。与先前的研究一致，1.5 atm FPI未引起海马或新皮层明显的神经元损失。然而，在胼胝体和丘脑中观察到强烈的炎症反应（如GFAP和Iba1免疫反应性增强所示）。弥散张量成像（DTI）后的分数各向异性彩色图显示，扣带FA值显著下降，该区域银浸渍增加，提示轴突损伤。在胼胝体和内外囊中也观察到银浸渍增加。这些发现与人类轻度TBI相关的缺陷和病理一致，并支持使用轻度FPI作为模型来评估假定的治疗方案。
The majority of people who sustain a traumatic brain injury (TBI) have an injury that can be classified as mild (often referred to as concussion). Although head CT scans for most subjects who have sustained a mild TBI (mTBI) are negative, these persons may still suffer from neurocognitive and neurobehavioral deficits. In order to expedite pre-clinical research and develop therapies, there is a need for well-characterized animal models of mTBI that reflect the neurological, neurocognitive, and pathological changes seen in human patients. In the present study, we examined the motor, cognitive, and histopathological changes resulting from 1.0 and 1.5 atmosphere (atm) overpressure fluid percussion injury (FPI). Both 1.0 and 1.5 atm FPI injury caused transient suppression of acute neurological functions, but did not result in visible brain contusion. Animals injured with 1.0 atm FPI did not show significant motor, vestibulomotor, or learning and memory deficits. In contrast, 1.5 atm injury caused transient motor disturbances, and resulted in a significant impairment of spatial learning and short-term memory. In addition, 1.5 atm FPI caused a marked reduction in cerebral perfusion at the site of injury that lasted for several hours. Consistent with previous studies, 1.5 atm FPI did not cause visible neuronal loss in the hippocampus or in the neocortex. However, a robust inflammatory response (as indicated by enhanced GFAP and Iba1 immunoreactivity) in the corpus callosum and the thalamus was observed. Examination of fractional anisotropy color maps after diffusion tensor imaging (DTI) revealed a significant decrease of FA values in the cingulum, an area found to have increased silver impregnation, suggesting axonal injury. Increased silver impregnation was also observed in the corpus callosum, and internal and external capsules. These findings are consistent with the deficits and pathologies associated with mild TBI in humans, and support the use of mild FPI as a model to evaluate putative therapeutic options.