Longhi Luca, Saatman Kathryn E, Fujimoto Scott, Raghupathi Ramesh, Meaney David F, Davis Jason, McMillan B S Asenia, Conte Valeria, Laurer Helmut L, Stein Sherman, Stocchetti Nino, McIntosh Tracy K
Traumatic Brain Injury Laboratory, Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Neurosurgery. 2005 Feb;56(2):364-74; discussion 364-74. doi: 10.1227/01.neu.0000149008.73513.44.
Repetitive concussive brain injury (CBI) is associated with cognitive alterations and increased risk of neurodegenerative disease.
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.
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 hours 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.
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.
重复性脑震荡性脑损伤（CBI）与认知改变及神经退行性疾病风险增加有关。
为评估脑震荡后脑易受二次脑震荡影响的时间窗，使用临床相关的CBI模型，对麻醉的小鼠进行假损伤或单次或重复性CBI（间隔3、5或7天）。评估认知、前庭和感觉运动功能（平衡和协调能力），并进行死后组织学分析以检测神经元变性、细胞骨架蛋白水解和轴突损伤。
假损伤动物或仅受过一次脑震荡的动物未观察到认知缺陷。与假损伤动物（P < 0.05）或接受单次脑震荡的小鼠（P < 0.01）相比，在3天或5天内遭受二次脑震荡的小鼠表现出明显受损的认知功能。当脑震荡间隔延长至7天时未观察到认知缺陷，这表明在初次脑震荡后的前5天内脑存在短暂易损性。尽管所有脑震荡小鼠均表现出短暂的运动缺陷，但间隔3天遭受两次脑震荡的组中前庭运动功能障碍更为明显（与所有其他组相比，P < 0.01）。尽管在所有遭受单次脑震荡的动物损伤后72小时至1周之间，在选择性脑区检测到散在的变性神经元、细胞骨架损伤证据和轴突损伤，但3天后发生二次脑震荡导致的创伤性轴突损伤（P < 0.05）比单次CBI导致的损伤明显更严重。
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，这些改变可能导致短暂的易损状态，在此期间3至5天内发生的二次脑震荡可导致更严重、更持久的轴突损伤和更严重的行为功能障碍。
