Persistent Blood-Brain Barrier Permeability in Post-Traumatic Epileptogenesis
Abstract
Epilepsy is a common long-term complication in patients who have experienced traumatic brain injury (TBI) that can develop in the weeks, years, or in some cases decades after an injury. Indeed, around 5% of all epilepsy is believed to be caused by TBI. Currently, there is little known about the ways in which traumatic brain injury can lead to the development of post-traumatic epilepsy (PTE). However, previous research suggests that bleeding in the brain may be an important risk factor for epilepsy. Moreover, in contrast with overt bleeding, it is increasingly recognized that TBI can also result in more subtle disruptions to blood vessels in the brain. This damage can result in the vessels becoming leaky or permeable, a problem that can persist in some individuals for months and years post-injury. This is particularly noteworthy given that leakage of toxic proteins from the blood into brain tissue has been associated with other forms of epilepsy. Our preliminary data suggest that complex and persistent brain pathologies can occur in some instances following TBI. This can include chronic leakage of the blood-brain barrier (BBB) – a complex structural and physiological barrier that controls when substances pass to and from the brain and peripheral blood circulation. To better understand how this process relates to the development of epilepsy (epileptogenesis), we propose to examine a unique in vivo model of TBI to (1) determine the potential relationship between persistent BBB permeability, the subsequent cellular uptake of serum proteins, and epileptogenesis; (2) determine the specific cellular mechanisms driving acute and chronic BBB permeability after TBI; and (3) evaluate the utility of advanced magnetic resonance imaging (MRI) approaches in the detection and evaluation of these pathological vascular changes. The development of epilepsy after TBI is a major health concern for civilian, military, and Veteran populations, and there is a clear and pressing need to better understand the evolving pathologies after TBI and identify potential targets for treatments. Here we propose a series of integrated studies to further understand how TBI-induced vascular pathologies relate to the development of epilepsy, with a view to identifying and mitigating these processes such that epileptogenesis is halted.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010838
Entities
People
- Victoria Johnson
Organizations
- United States Army
- University of Pennsylvania