Stroke and traumatic brain injury afflict more than 600,000 Americans annually, resulting in some level of functional impairment. While stroke afflicts primarily an adult population, traumatic brain injury affects mostly children and young adults. Variable recovery of function and some dysfunction will occur in most patients due to the innate ability of the nervous system to reorganize. This process is known as plasticity. Recent studies demonstrate a dramatic improvement in the speed and extent of behavioral recovery after brain injury by the use of the neurostimulant amphetamine. In contrast, phenytoin, a commonly administered antiseizure medication, retards recovery. Although the effects of these drugs have been demonstrated on behavioral recovery in both animal models and humans, their influence on mechanisms of plasticity remains largely unknown. The purpose of this project is to determine mechanisms that govern plasticity in a well-characterized rat model of cortical injury that results in a well-defined plastic response observed through functional optical imaging techniques. We propose to: * Evaluate the modulation by d-amphetamine (stimulant) and phenytoin (depressant) on functional cortical reorganization in the rat whisker/barrel cortex following a focal excitotoxic injury, utilizing intrinsic optical imaging. * Examine changes in gene expression that are associated with plasticity using """"""""gene chip"""""""" techniques in individual affected and spared cortical barrels to decipher the genetic response underlying observed functional outcomes and to gain insight into mechanisms by which d-amphetamine alters recovery following injury. * Determine whether structural alterations in the intra-cortical or thalamocortical connectivity correspond to observed functional changes using neural pathway tracing techniques. Functional imaging techniques allow us to determine the extent and time course of plastic changes in a longitudinal fashion. Our studies will elaborate critical aspects of cortical plasticity in terms of underlying gene expression, structural and functional reorganization following focal cortical injury. The determined responses will be modulated by pharmacologic agents in common clinical usage. The insight gained from these studies will help determine most effective management of patients to maximize recovery from brain injury.
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| Dubroff, J G; Stevens, R T; Hitt, J et al. (2005) Use-dependent plasticity in barrel cortex: intrinsic signal imaging reveals functional expansion of spared whisker representation into adjacent deprived columns. Somatosens Mot Res 22:25-35 |
