Center for Shock, Trauma and Anesthesiology Research (STAR) and Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Neurobiol Dis. 2013 Jun;54:252-63. doi: 10.1016/j.nbd.2012.12.017. Epub 2013 Jan 8.
Delayed secondary biochemical and cellular changes after traumatic brain injury continue for months to years, and are associated with chronic neuroinflammation and progressive neurodegeneration. Physical activity can reduce inflammation and facilitate recovery after brain injury. Here, we investigated the time-dependent effects, and underlying mechanisms of post-traumatic exercise initiation on outcome after moderate traumatic brain injury using a well-characterized mouse controlled cortical impact model. Late exercise initiation beginning at 5weeks after trauma, but not early initiation of exercise at 1week, significantly reduced working and retention memory impairment at 3months, and decreased lesion volume compared to non-exercise injury controls. Cognitive recovery was associated with attenuation of classical inflammatory pathways, activation of alternative inflammatory responses and enhancement of neurogenesis. In contrast, early initiation of exercise failed to alter behavioral recovery or lesion size, while increasing the neurotoxic pro-inflammatory responses. These data underscore the critical importance of timing of exercise initiation after trauma and its relation to neuroinflammation, and challenge the widely held view that effective neuroprotection requires early intervention.
创伤性脑损伤后的继发性生化和细胞变化会持续数月至数年，并与慢性神经炎症和进行性神经退行性变有关。身体活动可以减轻炎症并促进脑损伤后的恢复。在这里，我们使用一种经过充分验证的小鼠皮质撞击模型，研究了创伤后开始运动的时间依赖性影响及其对中度创伤性脑损伤后结果的潜在机制。与非运动损伤对照相比，延迟至损伤后 5 周开始运动（晚期运动），而非早期运动（1 周时），显著减少了 3 个月时的工作和记忆保留障碍，且减小了损伤体积。认知恢复与经典炎症途径的减弱、替代炎症反应的激活和神经发生的增强有关。相比之下，早期开始运动并不能改变行为恢复或损伤大小，反而增加了神经毒性促炎反应。这些数据强调了创伤后开始运动的时机及其与神经炎症的关系的重要性，挑战了有效神经保护需要早期干预的普遍观点。
