Acute Pharmacological Augmentation of Kv7 K+ Ion Channel Prevents Post-Traumatic Epilepsy and Chronic Traumatic Encephalopathy

Abstract

Seizures and development of epilepsy are common following various types of traumatic brain injury (TBI). Using a mouse model of blunt TBI, we recently showed that mice treated with the U.S. Food and Drug Administration (FDA)-approved antiepileptic drug, retigabine (RTG), have fewer seizures and much less brain damage within 7 days after trauma. Moreover, our pilot experiments suggest retigabine treatment after TBI may be protective against epilepsy development for over a year. In this project, we will test the effects of retigabine, and another newer drug in this class, RL648_81, in preventing two long-term impairments of brain trauma, epilepsy and dementia. We hope this work leads to the beginning of clinical trials, as this new treatment could help millions of people. Our treatment is based on the notion that brain trauma induces three key events that lead to a cascade of brain deficits, resulting in long-term impairment for the patient. These three key events are excessive activation of nerve cells, swelling of the brain, and loss of blood supply to regions of the brain. This project will use multiple advanced approaches to assess this possible new treatment for epilepsy and dementia after TBI. It will also elucidate the mechanism by which brain trauma induces epilepsy and dementia and if these changes are common for both chronic diseases.

Document Details

Document Type
DoD Grant Award
Publication Date
Dec 28, 2022
Source ID
W81XWH2210195

Entities

People

  • Fabio Antonio Borges Vigil

Organizations

  • United States Army
  • University of Texas Health Science Center at San Antonio

Tags

Fields of Study

  • Medicine
  • Psychology

Readers

  • Canadian European Scientific Immigration and Epilepsy Clearance Studies
  • Neurotrauma and Rehabilitation Medicine.
  • Traumatic Brain Injury (TBI) and Cognitive Aging in the Guam and Border Populations Affected by Alzheimer's Disease and Tau-Associated Dementias.