Department of Medicine, Melbourne Brain Centre, The University of Melbourne, Parkville, Victoria 3010, Australia.
J Neurotrauma. 2012 Jan 20;29(2):281-94. doi: 10.1089/neu.2011.2123. Epub 2011 Nov 8.
There is growing evidence that repeated brain concussion can result in cumulative and long-term behavioral symptoms, neuropathological changes, and neurodegeneration. Little is known about the factors and mechanisms that contribute to these effects. The current study addresses the need to investigate and better understand the effects of repeated concussion through the development of an animal model. Male Long-Evans rats received 1, 3, or 5 mild lateral fluid percussion injuries or sham injuries spaced 5 days apart. After the final injury, rats received either a short (24 h) or long (8 weeks) post-injury recovery period, followed by a detailed behavioral analysis consisting of tests for rodent anxiety-like behavior, cognition, social behavior, sensorimotor function, and depression-like behavior. Brains were examined immunohistochemically to assess neuroinflammation and cortical damage. Rats given 1, 3, or 5 mild percussion injuries displayed significant short-term cognitive impairments. Rats given repeated mild percussion injuries displayed significantly worse short- and long-term cognitive impairments. Rats given 5 mild percussion injuries also displayed increased anxiety- and depression-like behaviors. Neuropathological analysis revealed short-term neuroinflammation in 3-injury rats, and both short- and long-term neuroinflammation in 5-injury rats. There was also evidence that repeated injuries induced short- and long-term cortical damage. These cumulative and long-term changes are consistent with findings in human patients suffering repeated brain concussion, provide support for the use of repeated mild lateral fluid percussion injuries to study repeated concussion in the rat, and suggest that neuroinflammation may be important for understanding the cumulative and chronic effects of repeated concussion.
越来越多的证据表明,反复脑震荡会导致累积和长期的行为症状、神经病理学变化和神经退行性变。对于导致这些影响的因素和机制知之甚少。目前的研究通过开发动物模型来解决需要调查和更好地了解反复脑震荡影响的问题。雄性长耳大仓鼠接受 1、3 或 5 次轻度侧方液压冲击伤或假伤,间隔 5 天。最后一次受伤后,大鼠接受 24 小时或 8 周的短(24 小时)或长(8 周)伤后恢复期,随后进行详细的行为分析,包括测试啮齿动物的焦虑样行为、认知、社会行为、感觉运动功能和抑郁样行为。对大脑进行免疫组织化学检查以评估神经炎症和皮质损伤。接受 1、3 或 5 次轻度打击伤的大鼠表现出明显的短期认知障碍。接受重复轻度打击伤的大鼠表现出明显的短期和长期认知障碍加重。接受 5 次轻度打击伤的大鼠也表现出焦虑和抑郁样行为增加。神经病理学分析显示,3 次损伤大鼠有短期神经炎症,5 次损伤大鼠有短期和长期神经炎症。还有证据表明,反复损伤导致短期和长期皮质损伤。这些累积和长期变化与反复脑震荡患者的发现一致,为使用重复轻度侧方液压冲击伤研究大鼠的重复脑震荡提供了支持,并表明神经炎症可能对于理解反复脑震荡的累积和慢性影响很重要。