Accession Number:

ADA609622

Title:

Targeting Microglia to Prevent Post-Traumatic Epilepsy

Descriptive Note:

Final rept. 1 Jul 2011-30 Jun 2014

Corporate Author:

COLORADO UNIV AT BOULDER

Personal Author(s):

Report Date:

2014-07-01

Pagination or Media Count:

175.0

Abstract:

The purpose of this research project is to explore anti-epileptogenic strategies in and animal model of post-traumatic epilepsy PTE using lateral fluid percussion injury LFPI. Our focus is on attenuating damaging effects of hyperexcitability in the brain induced by inflammation resulting from glial cell immune responses to trauma. We are exploring two drugs, MN166 and SLC022, that are known to suppress post-traumatic glial activation and thus inflammation to evaluate their effectiveness in preventing epileptogenesis in the LFPI model of PTE. In the first project year we developed a high-speed videoEEG recording and analysis system for rapid quantification of chronically recorded epileptiform activity in multiple 24-32 subjects. With this system we became expert in identifying epileptiform versus normal videoEEG activity in the rodent and discovered an important source of artifact currently being interpreted in other published reports as seizure activity. We developed a pilocarpine model of temporal lobe epilepsy to explore the effectiveness of glial cell neuroimmune attenuation in preventing or limiting epileptogenesis development of epilepsy in this rapidly developing model. We explored numerous changes in the LFPI model to produce earlier developing signs of epilepsy, increasing the probability of succeeding in our long-term study of epileptogenesis following traumatic brain injury. Perhaps the most important outcome of this work was the negative finding that much published work concerning PTE with the LFPI model has not properly examined controls. Both injured and uninjured rats display spike-wave discharge SWD that, unlike previous reports, are not seizures. The actual incidence of seizures with LFPI may be extremely low, suggesting the need for a better model.

Subject Categories:

  • Medicine and Medical Research
  • Stress Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE