Probing the Mechanistic Role of Vascular Dysfunction and Vascular Inflammation in TBI-Mediated Cognitive Dysfunction

Traumatic brain injury (TBI) is a major cause of mortality/morbidity among service-members/veterans and is linked to long-term development of aging related dementia disorders through still poorly-defined mechanisms. We are testing the hypothesis that an important etiopathologic basis of TBI-related cognitive dysfunction is cerebrovascular dysfunction and vascular inflammation resulting in chronic brain hypoperfusion. We are also testing the hypothesis that TBI confers susceptibility to later development of cardiovascular risk factor(specifically diabetes/hyperglycemia)-related cerebrovascular dysfunction leading to cognitive impairment. In Aim 1 we will measure the cognitive function of Sprague-Dawley rats exposed to TBI by fluid percussion injury and determine the relationship with cerebrovascular function (in vivo by MRI and ex vivo by circle of Willis artery vasoreactivity) and vascular inflammation. In Aim 2 we will determine whether TBI and diabetes-related metabolic derangements or Beta-amyloid confer synergistic deleterious effects on cognitive function,cerebrovascular function and inflammation. We completed all rat cohorts which underwent TBI or sham operation and measured in-vivo and ex-vivo cerebrovascular function data. Our data show impaired cognitive function at 3 and 6 months following TBI with some regional association between cognitive and in vivo cerebrovascular function. Altered pial arterial smooth muscle function postangiotens in II was seen post-TBI. Induction of diabetes using streptozotocin did not lead to greater cognitive impairment in TBI rats.