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: 3.71).
08/2007; 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.
Available from: Boris Sabirzhanov
- "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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ABSTRACT: 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 5 weeks after trauma, but not early initiation of exercise at 1 week, significantly reduced working and retention memory impairment at 3 months, 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.
Available from: noninvasiveicp.com
- "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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ABSTRACT: Traumatic brain injury (TBI) may be due to a bump, blow, or jolt to the head or a penetrating head injury that disrupts normal brain function; it presents an ever-growing, serious public health problem that causes a considerable number of fatalities and cases of permanent disability annually. Physical exercise restores the healthy homeostatic regulation of stress, affect and the regulation of hypothalamic-pituitary-adrenal axis. Physical activity attenuates or reverses the performance deficits observed in neurocognitive tasks. It induces anti-apoptotic effects and buttresses blood-brain barrier intactness. Exercise offers a unique non-pharmacologic, non-invasive intervention that incorporates different regimes, whether dynamic or static, endurance, or resistance. Exercise intervention protects against vascular risk factors that include hypertension, diabetes, cellular inflammation, and aortic rigidity. It induces direct changes in cerebrovasculature that produce beneficial changes in cerebral blood flow, angiogenesis and vascular disease improvement. The improvements induced by physical exercise regimes in brain plasticity and neurocognitive performance are evident both in healthy individuals and in those afflicted by TBI. The overlap and inter-relations between TBI effects on brain and cognition as related to physical exercise and cognition may provide lasting therapeutic benefits for recovery from TBI. It seems likely that some modification of the notion of scaffolding would postulate that physical exercise reinforces the adaptive processes of the brain that has undergone TBI thereby facilitating the development of existing networks, albeit possibly less efficient, that compensate for those lost through damage.
Available from: ncbi.nlm.nih.gov
- "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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ABSTRACT: Certain dietary factors, such as omega-3 fatty acids and curcumin, are reviewed in their context of stimulating molecular systems that serve synaptic function, while diets rich in saturated fats do the opposite. In turn, exercise, using similar mechanisms as healthy diets, displays healing effects on the brain such as counteracting the mental decline associated with age and facilitating functional recovery resulting from brain injury and disease. Diet and exercise are two noninvasive approaches that used together may enhance neural repair. Omega 3 fatty acids and curcumin elevate levels of molecules important for synaptic plasticity such as brain-derived neurotrophic factor (BDNF), thus benefiting normal brain function and recovery events following brain insults.
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