Experience-dependent neuroplasticity in the perilesion cortex after focal cortical infarcts in rats
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The leading cause of long-term disability among adults in industrialized countries is stroke. Exploration of the brain mechanisms involved during recovery from stroke is likely to yield information that can be used to promote better functional outcome. After focal motor cortical infarcts, reorganization of movement representations in the remaining motor cortex has been linked to both spontaneous recovery and recovery induced by rehabilitative training. However, the mechanisms and nature of cortical reorganization remain poorly understood. The central hypothesis of these dissertation studies is that synaptogenesis and structural reorganization in the cortex near the lesion are linked to spontaneous partial recovery and the beneficial effects of motor rehabilitative training after stroke-like injury. This was tested in a rat model of focal cortical ischemia by both behavioral and neuroanatomical measures in perilesion cortex. In separate studies, it was found that motor rehabilitative training on a skilled reaching task using the impaired forelimb after a unilateral ischemic lesion improved forelimb functional outcome and facilitated synaptogenesis in perilesion cortex. In addition, this improved functional recovery was disrupted by focal protein synthesis inhibition in perilesion cortex, suggesting the structural plasticity in this area plays an important role in regained function. Finally, it was also hypothesized that a therapy that enhances the efficacy of motor rehabilitation also enhances synaptic structural plasticity in perilesion cortex. Cortical electrical stimulation (CS) during motor rehabilitation has previously been shown to improve the efficacy of rehabilitation. Increased density of axodendritic synapses in perilesion cortex was found in rats that received cortical electrical stimulation of perilesion cortex during rehabilitation compared to rehabilitation alone, and the synaptic density was positively correlated with post-rehabilitation reaching performance. These findings suggest that CS-induced functional improvements may be mediated by synaptic structural plasticity in stimulated cortex. Together these studies indicate that, after a cortical lesion in rats, motor rehabilitation alone or in conjunction with other efficacious therapies can greatly enhance synaptic structural plasticity in perilesion cortex. Furthermore, these studies suggest that rehabilitation induced improvements in functional outcome are dependent upon the structural and functional integrity of the reorganized perilesion cortex.