Accession Number:

AD1111570

Title:

Probing the mechanistic role of vascular dysfunction and vascular inflammation in TBI-mediated cognitive dysfunction

Descriptive Note:

[Technical Report, Annual Report]

Corporate Author:

CARL T. HAYDEN MEDICAL RESEARCH FOUNDATION

Personal Author(s):

Report Date:

2020-08-01

Pagination or Media Count:

25

Abstract:

Traumatic brain injury TBI is a major cause of mortalitymorbidity among service-membersveterans 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 diabeteshyperglycemia-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 the rat cohorts which underwent TBI or sham operation and measured in-vivo and ex-vivo cerebrovascular function data. Our data so far show impaired cognitive function at 3 and 6 months following TBI with some regional association between cognitive and in vivo cerebrovascular function and modest reduction in pial arterial smooth muscle dependent function post-TBI. Induction of diabetes using streptozotocin did not lead to greater cognitive impairment in TBI rats.

Descriptors:

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

[A, Approved For Public Release]