JaK/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis
Abstract
Our proposal tests the hypothesis that JaK/STAT pathway activation after TBI leads to Gabra1 repression and is a critical mediator of post-traumatic epileptogenesis and epilepsy progression, and that inhibition of this pathway at the time of TBI and/or after development of post-traumatic epilepsy will inhibit epilepsy development and/or progression after CCI. In the first year of funding, equipment and training necessary to perform the CCI model was obtained at University of Colorado, and CCI was successfully performed in mice at both institutions. Training was completed for all personnel on all necessary molecular, anatomical, electrophysiological and neurophysiological (EEG) techniques, essential baseline data was obtained in the mouse CCI model, and specific outcome measures were established. Moreover, issues with the JAK/STAT3 inhibitor (WP1066) have been mitigated and the drug is now successfully used in all labs. Additional optimization of the WP1066 dosing protocol is underway and is expected to be completed very soon. Two manuscripts and three abstracts related to GABA(A) receptor, JAK/STAT pathway and cell death alterations following TBI were published during the funding period.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 31, 2013
- Accession Number
- ADA612534
Entities
People
- Amy Brooks-kayal
- Bret Smith
Organizations
- University of Colorado Boulder