Probing the Mechanistic Role of Vascular Dysfunction and Vascular Inflammation in TBI-Mediated Cognitive Dysfunction
Abstract
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 -amyloid confer synergistic deleterious effects on cognitive function, cerebrovascular function and inflammation. We completed the first 2 cohorts who underwent injury or sham treatment and obtained 6-month cognitive function and in-vivo and ex-vivo cerebrovascular function data, but our data remains preliminary and incomplete. Preliminary data so far are consistent with our hypothesis of delayed cognitive dysfunction following TBI, but we advise caution in interpretation due to incomplete data.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 31, 2018
- Accession Number
- AD1059198
Entities
People
- Jonathan Lifshitz
- Raymond Q. Migrino