Development and Characterization of a Novel Model to Study Refractory Status Epilepticus
Abstract number :
2.175
Submission category :
3. Neurophysiology / 3F. Animal Studies
Year :
2024
Submission ID :
98
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Melissa l. Blotter, BS – Brigham Young University
Jacob Norby, BS candidate – Brigham Young University
Jacob Norby, BS candidate – Brigham Young University
Jacob B. Cahoon, BS candidate – Brigham Young University
Maxwell Holmes, BS candidate – Brigham Young University
Micah R. Shepherd, PhD – Brigham Young University
R. Ryley Parrish, PhD – Brigham Young Univerisity
Rationale: Status epilepticus (SE) is a seizure state characterized by continuous ictal activity lasting over 5 minutes in duration. SE frequently becomes unresponsive to frontline antiepileptic drugs (AEDs). This is known as refractory status epilepticus (RSE), a neurological medical emergency with a mortality rate that some studies have found to be as high as 38%. Understanding the differences in brain region recruitment to SE may help elucidate the mechanisms underlying SE and its refractory nature. We aim to study the spatiotemporal aspects of this activity with high resolution to shed light on mechanisms of both SE genesis and propagation, as well as see the effects of AEDs on these propagation patterns.
Methods: Acute mice brain slices were sliced into 350 µm thick slices and were placed on a 3Brain complementary metal oxide semiconductor high-density multi-electrode array (CMOS-HD-MEA) with 4,096 recording channels at a spacing of 60 µm. Slices were bathed with either aCSF containing 4-aminopyridine (4AP) or aCSF without Mg2+ ions, to induce seizureepileptic-like activity. The activity was recorded for 3, one-hour recordings. Data were sampled at 2,000 Hz with 1.0 Hz high pass filtering and no low pass filtering. The recorded data was then run through a graphic user interface (GUI) developed in our lab and the spatiotemporal aspects were analyzed.
Results: The results demonstrate that the neocortex can be experiencing status epilepticus-like activity and self-terminating seizure-like activity simultaneously in different subregions. We will also show that over time there can be a progression of SE across subregions, demonstrated by our novel SE mapping toolbox. We are actively exploring how AED affects the propagation patterns of SE in our developed model.
Conclusions: We anticipate that our findings will translate into a powerful new model that will provide new insights into understanding SE and RSE mechanisms. Insight into the mechanisms of SE propagation patterns can lead to the discovery of new and effective treatments of RSE.
Funding: Funding was provided by American Epilepsy Society and Brigham Young University College of Life Sciences
Neurophysiology