Epilepsy

Our epilepsy research focuses on how chloride cotransporters, particularly NKCC1, drive the hyperexcitability that underlies chronic epilepsy. Using a rat model of pilocarpine-induced temporal lobe epilepsy, we combine in vitro hippocampal electrophysiology with EEG recordings to characterize how altered chloride dynamics compromise GABAergic inhibition in dentate gyrus granule cells and at the axon initial segment of pyramidal neurons — a site we have shown plays a distinctive role in controlling neuronal excitability.

This mechanistic work has directly guided translational studies, including our finding that bumetanide, an NKCC1 inhibitor, enhances the antiepileptic effect of conventional drugs such as phenobarbital, and more recent work evaluating c-Abl inhibition as a way to reduce neuronal damage and seizure severity.