Mild head injury increasing the brain's vulnerability to a second concussive impact

Mild head injury increasing the brain's vulnerability to a second concussive impact
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DOI:
10.3171/jns.2001.95.5.0859
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发表时间:
2001-11-01
影响因子:
4.1
通讯作者:
McIntosh, TK
McIntosh, TK
中科院分区:
医学1区
文献类型:
--
作者:
Laurer, HL;Bareyre, FM;McIntosh, TK

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Object.轻度创伤性重复性脑损伤(RHI)可导致神经行为障碍,并与神经退行性疾病的早期发作相关。作者开发了一种动物模型来研究与RHI相关的行为和病理变化。成年雄性C57 BL/6小鼠经受单一损伤(43只小鼠)、重复损伤(间隔49分钟24小时的两次损伤)或无冲击(36只小鼠)。使用Morris水迷宫测试评估认知功能,使用神经评分、旋转棒和旋转杆测试的电池评估神经运动功能。还评价了脑创伤后1天至56天之间的心血管变化、血脑屏障(BBB)破坏、创伤性轴突损伤以及神经退行性和组织病理学变化。在任何组中均未检测到认知功能障碍。单次撞击组仅在伤后3天显示轻度损伤,而RHI在第二次损伤后3天和7天引起明显的缺陷。此外,RHI在旋转杆和旋转杆测试期间导致功能障碍,这在单次撞击后的任何动物中均未观察到。在单一脑损伤后观察到的小面积皮质血脑屏障破裂和轴突损伤在RHI后严重加重。微管相关蛋白-2的免疫组织化学染色显示,只有在动物进行RHI的免疫反应性显着的区域损失。在任何脑损伤动物中均未观察到β-淀粉样蛋白或tau蛋白沉积。根据他们的研究结果,作者认为,在轻度脑外伤的最初发作后至少24小时内,大脑对第二次创伤性损伤的脆弱性增加。
Object. Mild, traumatic repetitive head injury (RHI) leads to neurobehavioral impairment and is associated with the early onset of neurodegenerative disease. The authors developed an animal model to investigate the behavioral and pathological changes associated with RHI.Methods. Adult male C57BL/6 mice were subjected to a single injury (43 mice), repetitive injury (two injuries 24 hours apart 49 m ice), or no impact (36 mice). Cognitive function was assessed using the Morris water maze test, and neurological motor function was evaluated using a battery of neuroscore, rotarod, and rotating pole tests. The animals were also evaluated for cardiovascular changes, blood-brain barrier (BBB) breakdown, traumatic axonal injury, and neurodegenerative and histopathological changes between 1 day and 56 days after brain trauma. No cognitive dysfunction was detected in any group. The single-impact group showed mild impairment according to the neuroscore test at only 3 days postinjury, whereas RHI caused pronounced deficits at 3 days and 7 days following the second injury. Moreover, RHI led to functional impairment during the rotarod and rotating pole tests that was not observed in any animal after a single impact. Small areas of cortical BBB breakdown and axonal injury, observed after a single brain injury, were profoundly exacerbated after RHI. Immunohistochemical staining for microtubule-associated protein-2 revealed marked regional loss of immunoreactivity only in animals subjected to RHI. No deposits of beta -amyloid or tau were observed in any brain-injured animal.Conclusions. On the basis of their results, the authors suggest that the brain has an increased vulnerability to a second traumatic insult for at least 24 hours following an initial episode of mild brain trauma.