Molecular and clinical aspects of blood-brain barrier dysfunction in traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. TBI ranges from mild to severe, with concussion being considered a form of mild TBI (mTBI). Long-term issues, such as cognitive impairment and psychological issues have been shown to be associated with TBI exposure. The exact mechanism behind these long-term consequences is not fully understood. The blood-brain barrier (BBB) is made of up a number of different components which line the blood vessels in the brain. It is a selective barrier which helps tightly regulate the microenvironment within the brain to allow it to function normally. The BBB has been shown to be disrupted following TBI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive method which allows us to examine the integrity of the BBB. Using DCE-MRI, we have examined two rare genetic conditions with associated BBB dysfunction in order to better understand how the specific genetic variations impact BBB integrity and how these underlying mechanisms might relate to BBB dysfunction in TBI. Employing the same techniques, we also conducted research focused on (1) long-term neuropsychological and BBB outcomes in retired contact sport athletes who have been exposed to repetitive mTBI and (2) long-term neuropsychological and BBB outcomes in individuals who have been exposed to moderate-severe TBI.