Griesbach Grace S, Gómez-Pinilla Fernando, Hovda David A
Division of Neurosurgery, University of California-Los Angeles (UCLA), Los Angeles, California, USA.
J Neurotrauma. 2007 Jul;24(7):1161-71. doi: 10.1089/neu.2006.0255.
We recently found that an exercise-induced increase in hippocampal brain-derived neurotrophic factor (BDNF) is dependent when exercise is initiated after traumatic brain injury (TBI). When voluntary exercise was delayed by 2 weeks after a mild fluid-percussion injury (FPI) in rats, an increase in BDNF and an improvement in behavioral outcome were observed. This suggests that following FPI there is a therapeutic window for the implementation of voluntary exercise. To determine if more severely injured animals require more time after TBI before voluntary exercise can increase neuroplasticity, adult male rats with a moderate lateral FPI or sham injury were housed with or without access to a running wheel from post-injury-day (PID) 0-6, 14-20 or 30-36. Rats with a mild injury only had access to the running wheel from PID 0-6 or 14-20. Rats were sacrificed at PID 7, 21, or 37. BDNF, synapsin I, and cyclic AMP response element binding protein (CREB) were analyzed within the ipsilateral hippocampus. Whereas BDNF levels significantly increased with exercise in the mild FPI rats that were exercised from PID 14 to 20, the moderate FPI rats only showed significant increases in BDNF when exercised from PID 30 to 36. In addition, moderate FPI rats that were allowed to exercise from PID 30 to 36 also exhibited significant increases in synapsin I and CREB. These results indicate that the time window for exercise-induced increases in BDNF, synapsin I, and CREB is dependent on injury severity.
我们最近发现，运动诱导的海马脑源性神经营养因子（BDNF）增加取决于创伤性脑损伤（TBI）后开始运动的时间。当大鼠轻度液体冲击伤（FPI）后自愿运动延迟2周时，观察到BDNF增加和行为结果改善。这表明FPI后存在一个实施自愿运动的治疗窗口。为了确定更严重受伤的动物在TBI后是否需要更多时间才能使自愿运动增加神经可塑性，将成年雄性大鼠中度侧方FPI或假手术损伤后，从损伤后第0天至第6天、第14天至第20天或第30天至第36天，分别饲养在有或没有跑步机的环境中。仅轻度损伤的大鼠在损伤后第0天至第6天或第14天至第20天可以使用跑步机。在损伤后第7天、第21天或第37天处死大鼠。分析同侧海马内的BDNF、突触素I和环磷酸腺苷反应元件结合蛋白（CREB）。虽然从损伤后第14天至第20天进行运动的轻度FPI大鼠中，BDNF水平随运动显著增加，但中度FPI大鼠仅在从损伤后第30天至第36天进行运动时，BDNF才显著增加。此外，从损伤后第30天至第36天允许运动的中度FPI大鼠，其突触素I和CREB也显著增加。这些结果表明，运动诱导BDNF、突触素I和CREB增加的时间窗口取决于损伤的严重程度。
