Temporal window of vulnerability to repetitive experimental concussive brain injury
Temporal window of vulnerability to repetitive experimental concussive brain injury
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DOI：
10.1227/01.neu.0000149008.73513.44
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发表时间：
2005-02-01
期刊：
影响因子：
4.8
通讯作者：
McIntosh, TK
中科院分区：
文献类型：
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作者：
Longhi, L;Saatman, KE;McIntosh, TK
目的：反复脑震荡损伤(CBI)与认知改变和神经退行性疾病的风险增加有关。方法：采用临床相关的CBI模型，对麻醉小鼠造成假损伤或单次或重复脑损伤(相隔3、5或7天)，以评估脑震荡对第二次脑震荡的易感性的时间窗口。评估认知、前庭和感觉运动功能(平衡和协调)，并进行死后组织学分析，以检测神经元变性、细胞骨架蛋白分解和轴突损伤。结果：假损伤和一次性脑震荡动物均未观察到认知功能障碍。与假损伤小鼠(P<；0.05)或单次脑震荡小鼠(P<；0.01)相比，在3或5天内再次脑震荡的小鼠表现出显著的认知功能受损。当脑震荡间隔延长到7天时，没有观察到认知障碍，这表明在最初脑震荡后的头5天里，大脑存在一过性的脆弱性。虽然所有脑震荡小鼠都表现出一过性运动障碍，但在相隔3天持续两次脑震荡的组中，前庭运动功能障碍更为明显(P<；0.01与所有其他组相比)。虽然在所有单次脑震荡的动物伤后72-1周内，在选择性脑区发现了散在的变性神经元、细胞骨架损伤和轴突损伤的证据，但3天后第二次脑震荡的发生导致的创伤性轴突损伤明显大于单次脑震荡所致的外伤性轴突损伤(P<；0.05)。结论：这些数据表明，单次脑震荡与行为功能障碍和亚细胞改变有关，这可能导致短暂的脆弱状态，在此期间，3-5天内的第二次脑震荡可导致更严重和更持久的轴突损伤和更大的行为功能障碍。
OBJECTIVE: Repetitive concussive brian injury (CBI) is associated with cognitive alterations and increased risk of neurodegenerative disease.METHODS: To evaluate the temporal window during which the concussed brain remains vulnerable to a second concussion, anesthetized mice were subjected to either sham injury or single or repetitive CBI (either 3, 5, or 7 days apart) using a clinically relevant model of CBI. Cognitive, vestibular, and sensorimotor function (balance and coordination) were evaluated, and postmortem histological analyses were performed to detect neuronal degeneration, cytoskeletal proteolysis, and axonal injury.RESULTS: No cognitive deficits were observed in sham-injured animals or those concussed once. Mice subjected to a second concussion within 3 or 5 days exhibited significantly impaired cognitive function compared with either sham-injured animals (P < 0.05) or mice receiving a single concussion (P < 0.01). No cognitive deficits were observed when the interconcussion interval was extended to 7 days, suggestive of a transient vulnerability of the brain during the first 5 days after an initial concussion. Although all concussed mice showed transient motor deficits, vestibulomotor dysfunction was more pronounced in the group that sustained two concussions 3 days apart (P < 0.01 compared with all other groups). Although scattered degenerating neurons, evidence of cytoskeletal damage, and axonal injury were detected in selective brain regions between 72 and 1 week after injury in all animals sustaining a single concussion, the occurrence of a second concussion 3 days later resulted in significantly greater traumatic axonal injury (P < 0.05) than that resulting from a single CBI.CONCLUSION: These data suggest that a single concussion is associated with behavioral dysfunction and subcellular alterations that may contribute to a transiently vulnerable state during which a second concussion within 3 to 5 days can lead to exacerbated and more prolonged axonal damage and greater behavioral dysfunction.