Neuron-Selective Neuromodulation and TRPC Ion Channel Targeting for Prevention of Trauma-Induced Temporal Lobe Epilepsy
Abstract
The proposed research is for an Epilepsy Research Program Idea Development Award at the University of Texas Health Science Center San Antonio to identify new ways to understand and prevent epilepsy after brain trauma. Our research project has the translational goal of identifying the underlying cause of epileptic seizures after traumatic brain injury. This research will expand the identification of how the brain can be protected after traumatic brain injury and to prevent the process of epilepsy and associated neurological damage from spreading throughout the brain. The main target of this research is the protection of neuronal cells, which are provoked after trauma and produce the uncontrolled electrical activity of seizures. Our central hypothesis is that a type of excitatory ion channel is selectively increased in activity after traumatic brain injury, contributing to a greater chance of seizures. By blocking this channel activity, we hypothesize that the progression of epilepsy can be halted before it takes hold of the brain. We have shown that experimental drugs that block this electrical activity can reduce seizures in non-traumatic epilepsy models, but there has been no investigation of this pathway in the contribution to post-traumatic epilepsy. We propose a multidisciplinary approach of (1) analyzing the mechanism of harmful neuronal changes after injury and (2) quieting the neuronal activity with selective therapeutics that will synergistically reduce the development of epilepsy. We will use a mouse model that simulates blunt trauma to test our hypothesis, which is new territory for studying this group of ion channel proteins that have been shown to contribute to development of epilepsy. The focus of this preclinical research is to examine early detection markers after trauma and determine both mechanisms of epilepsy progression and how to stop it. This project has long-term potential to achieve clinically relevant outcomes for the improved treatment of victims of traumatic brain injury to prevent the spread of seizures and epilepsy.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910400
Entities
People
- Chase Carver
Organizations
- United States Army
- University of Texas Health Science Center at San Antonio