Role of Contra-lesional Cortex in Recovery of Function After Traumatic Brain Injury

Traumatic brain injury (TBI) remains a devastating condition for which treatment is difficult considering the many unknown underlying endogenous brain mechanisms that interact after injury. The contralesional cortex has been shown to change behavior after injury and is an interesting mechanistic player for targeted therapeutic treatment. Functional MRI data from our lab show considerable contralesional “wrong side” activation at one week post-injury when stimulating the affected limb and a much greater BOLD response of the contralesional cortex at 4 weeks post injury when stimulating the unaffected forelimb. In vivo electrophysiological experiments from our lab show hyperexcitability in the contralesional cortex at 4 weeks post-injury. Given this data, we will test the hypothesis that the contralesional cortex has different roles in functional recovery at specific time points after injury, specifically by inhibiting activation in the ipsilesional cortex thereby reducing the extent of Hebbian plasticity in ipsilesional functional recovery. Using immunohistochemistry techniques, we will stain for c-Fos positive cells in brain sections of rats of varying injury severity to test if this larger BOLD response, or hyperexcitability of the contralesional cortex, stems from less inhibitory signals from the ipsilesional cortex. We will also stain sections for specific GABA receptor sub-types to investigate the relation between activity and inhibitory markers in rat models after TBI.  In the contralesional cortex, we anticipate an up-regulation of c-Fos positive cells and a down-regulation of contralesional inhibitory receptor sub-types, while in the ipsilesional cortex we expect a corresponding increase in ipsilesional inhibitory markers at 4 weeks post-injury.