Targeting Microglia to Prevent Post-Traumatic Epilepsy
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 this first project year we have developed a high-speed video/EEG recording and analysis system for rapid quantification of chronically recorded epileptiform activity in multiple (24-32) subjects. With this system we have become expert in identifying epileptiform versus normal video/EEG activity in the rodent and have discovered an important source of artifact currently being interpreted in other published reports as seizure activity. We have 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 are making changes in our 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. Finally, we discovered and published results concerning development of post-traumatic anxiety in our brain injured animals that we could effectively prevent with peri-injury administration of glial attenuating drug, MN-166, the same drug to be used in our studies concerning prevention of epileptogenesis following traumatic brain injury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA568661
Entities
People
- Daniel S Barth
Organizations
- University of Colorado Boulder