Authors: Isaac Stubbs, Skyler Russell, Melissa Blotter, Maxwell Holmes
Mentors: Ryley Parrish
Insitution: Brigham Young University
Status Epilepticus (SE) is a severe medical condition marked by continuous seizures lasting over 5 minutes. When SE becomes resistant to anticonvulsant drugs, the condition is known as Refractory Status Epilepticus (RSE), which lacks effective treatments and has a mortality rate of 38%. RSE lacks effective treatments partially due to our limited understanding of the mechanisms that lead to patient drug resistance to commonly used anticonvulsants. This study aims to address this knowledge gap in two pivotal ways.
First, we have employed a high-density multi-electrode array (HD-MEA) with acute mouse brain slices to better understand RSE propagation patterns and various seizure states with unparalleled spatial precision. The HD-MEA allows us to record from the entire brain slice with 4096 electrodes sampling electrophysiological activity at every 60 micrometers for many hours at a time. Our data demonstrates that different seizure states, such as phasic seizure-like events, short duration epileptic discharges, or RSE itself, occur within both the same brain region and in different brain regions simultaneously. With our novel data visualization software, we can visualize the unique propagation of this phenomenon. These findings indicate that RSE might be a progressive event, challenging conventional understanding of RSE.
Second, we are currently exploring a potential pharmacoresistance mechanism that may contribute to the patient entering RSE, which suggests that changes in the chloride reversal potential may lead to a phenomenon known as depolarizing GABA. Depolarizing GABA may negate the effectiveness of the currently used antiepileptic drugs that rely on standard physiological chloride conductance to effectively limit seizure activity. We are studying this drug resistant mechanism with the HD-MEA by introducing anticonvulsant drugs to acute mouse brain slices during the evolution of RSE to locate a critical point at which the slice becomes resistant to these compounds.
We hope this study will illuminate the complexities of RSE by revealing its progressive nature and drug resistant properties.