Probing the Mechanistic Role of Vascular Dysfunction and Vascular Inflammation in TBI-Mediated Cognitive Dysfunction
Abstract
Traumatic brain injury (TBI) is associated with later development of impaired cognitive function and dementia. The mechanisms underlying this relationship remain largely unknown. TBI causes early and late impairment of cerebrovascular function, much in the same way that dementia disorders such as Alzheimer?s disease and vascular dementia were associated with early development of impaired vascular function. Our overall goal is to test the hypothesis that the cerebrovascular dysfunction induced by TBI leads to later development of impaired cognitive function in rats. We will also look at underlying mechanisms by which TBI induces impaired cerebrovascular function focusing on the role of oxidative stress and vascular inflammation. We will determine if TBI early in life modulates the effects by which type 2 diabetes impairs cerebrovascular and cognitive function. We will use a validated model of diffuse TBI in rats using fluid percussion injury. We will measure cognitive function using novel object recognition tasks. We will measure cerebrovascular function in living animals using magnetic resonance imaging (MRI) and by measuring reactivity of blood vessels isolated from the brain. We will determine the relationship between cerebrovascular function and cognitive function and evaluate whether pretreatment with lipopolysaccharide, a chemical that is known to improve cerebrovascular function, will attenuate the effects of TBI. In some rats that had TBI, we will induce development of diabetes using streptozotocin and compare cerebrovascular and cognitive function against diabetic rats without TBI. The proposal is significant in filling in our knowledge gaps about how TBI causes impaired cognitive function as well as understanding the underlying causes on how TBI induces impaired cerebrovascular function. If successful, the study will uncover important new treatment pathways that could be used to prevent impaired cognitive and cerebrovascular function following TBI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710473
Entities
People
- Raymond Migrino
Organizations
- Phoenix VA Health Care System
- United States Army