The upregulation of plasticity-related proteins following TBI is disrupted with acute voluntary exercise.Brain Res. 2004 Aug 06; 1016(2):154-62.BR
Following traumatic brain injury (TBI), the brain undergoes a period of metabolic and neurochemical alterations that may compromise the reactivity of neuroplasticity-related molecular systems to physiological stimulation. In order to address the molecular mechanisms underlying plasticity following TBI and the effects of physical stimulation in the acute phase of TBI, levels of intracellular signaling molecules were assessed following voluntary exercise. Lateral fluid percussion injury (FPI) and sham-operated (Sham) rats were housed with or without access to a running wheel (RW) from postsurgery day 0 to 6. Parietal and occipital cortical tissues were analyzed for brain-derived neurotrophic factor (BDNF) using an enzyme-linked immunoabsorbant assay (ELISA). In addition, synapsin I, phospho-synapsin I, cyclic-AMP response-element-binding protein (CREB), phospho-CREB, calcium-calmodulin-dependent protein kinase II (CAMKII), mitogen-activated protein (MAP) kinase I and II (MAPKI and MAPKII), and protein kinase C (PKC) were analyzed by western blot. Results from this study indicated that FPI alone lead to significant increases in synapsin I, CAMKII, and phosphorylated (P) MAPKI (p44) and MAPKII (p42). Exercise in the sham operates led to significant cortical increases of CREB and synapsin I. However, in the FPI rats, the response to exercise was opposite to that seen in the shams in that exercise resulted in significant decreases of CREB, synapsin I, PKC, CAMKII, MAPKI, and MAPKII. Indeed, all the observed proteins in the acutely exercised FPI rats tended to be lower compared to the FPI sedentary (Sed) rats. These results indicate that intracellular signaling proteins are increased during the first week following FPI and that premature voluntary exercise may compromise plasticity.