JaK/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis
Annual rept. 1 Jul 2012-30 Jun 2013
COLORADO UNIV AURORA CO
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Our proposal tests the hypothesis that JaKSTAT 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 andor after development of post-traumatic epilepsy will inhibit epilepsy development andor 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 JAKSTAT3 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 GABAA receptor, JAKSTAT pathway and cell death alterations following TBI were published during the funding period.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research