In the proposed studies, I intend to characterize diffuse TBI (traumatic brain injury) at different developmental ages by addressing the pathophysiological processes and cell death phenotype at each age. My studies are intended to address the following hypothesis: mechanisms of cell death after diffuse TBI differ as a function of developmental age.
Specific Aim #1 proposes to characterize a new diffuse traumatic brain injury model in rats ranging from 7 days through 3 months of age.
This aim i s to determine differences with regard to cell death phenotype and key related molecular mechanisms as well as functional outcomes as a function of developmental age. I will test the predictions that 1) diffuse TBI in young rats favors molecular mechanisms associated with caspase dependent apoptosis, 2) diffuse TBI in adult rats favors molecular mechanisms associated with necrosis, and 3) diffuse TBI will result in deficits in functional outcomes that are dependent upon developmental age.
Specific Aim #2 proposes to address this hypothesis by studying the effects of treatment with caspase inhibitors or magnesium salts on cell death and functional outcome according to developmental age.
This aim i s to determine if caspase inhibitors or magnesium salts can protect against diffuse TBI in young rats. We will test the prediction that caspase inhibitors, but not magnesium salts, will decrease damage and neurological deficits induced by diffuse TBI in young rats.
