Article

Time window for voluntary exercise-induced increases in hippocampal neuroplasticity molecules after traumatic brain injury is severity dependent

Division of Neurosurgery, University of California-Los Angeles (UCLA), Los Angeles, California, USA.
Journal of Neurotrauma (Impact Factor: 3.97). 08/2007; 24(7):1161-71. DOI: 10.1089/neu.2006.0255
Source: PubMed

ABSTRACT 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.

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    • "A decrease in free intracellular magnesium concentration also occurs after TBI and is associated with a reduction in cellular bioenergetics state that reflects injury severity (Vink et al., 1988a, 1988b). Given that exercise itself places an increased energetic demand, it has been suggested that injury severity may thus critically affect the consequences of physical activity timing (Griesbach et al., 2007). In contrast, others have proposed that hypermetabolism rather than hypometabolism may be a key issue. "
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    • "Lombardi (2008) has discussed the relative therapeutic effects of psychostimulant drugs co-administered with sensory–motor exercise inventions that have been shown to induce a steady acceleration of motor recovery in TBI laboratory animals; this improvement in turn is considered to exert a facilitation of the neurological recovery process. Griesbach et al. (2007) have demonstrated that an exercise-induced increase in hippocampal BDNF is dependent upon when the exercise schedule is initiated after TBI. They had observed that the introduction of voluntary exercise Fig. 1 "
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    • "More specifically, exercise plays an important role in the maintenance of the synaptic structure (Vaynman et al., 2004), axonal elongation (Molteni et al., 2004), and neurogenesis in the adult brain (van Praag et al., 1999). Exercise applied after experimental traumatic brain injury has also been shown to have beneficial effects but these effects seem to depend on the post-injury resting period and the severity of the injury(Griesbach et al., 2007). "
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