Microvascular injury and blood-brain barrier dysfunction as novel biomarkers and targets for treatment in traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of death and disability around the world. While long-term neurological and cognitive complications and disability are a major concern,to this date there are no means to accurately predict such complications nor therapies for their prevention. An emerging consensus points to the critical importance of including new means for the identification of brain pathological events in order to allow efficient prevention. In this proposal we address this unmet need by investigating traumatic microvascular injury (TMI), an established but understudied TBI pathology with a potential as a candidate diagnostic biomarker and therapeutic target. Blood-brain barrier (BBB) dysfunction is a prominent feature of TMI and often obtained in animal TBI models as well as in human pathological specimens. The BBB is a unique structural and functional barrier allowing the normal function of the nervous system. Our previous studies confirmed a direct role for BBB pathology in inducing brain dysfunction and damage. The goals of this research are (1) to test a new imaging approach to detect, localize, and track BBB pathology in animal models of TBI; (2) to test new therapeutics that target TMI and follow BBB pathology; and (3) implement a similar imaging approach in humans to evaluate the prevalence and spatio-temporal dynamics of BBB pathology in human subjects after acute TBI. We strongly believe that the proposed pre-clinical and translational approach will result in the first objective,quantitative and reliable diagnostic approach for the identification of TMI.