Robust Induction of Spontaneous Recurrent Seizures and Hippocampal Sclerosis with Synthetic Kainic Acid in the Intrahippocampal Kainate Model
- 1Massachusetts General Hospital
Abstract
Intrahippocampal kainate (IHK) is a well-established mouse model of temporal lobe epilepsy, in which focal hippocampal injection of kainic acid induces excitotoxic injury followed by the development of chronic spontaneous seizures. Commercial sources of kainic acid (KA) have increasingly transitioned from naturally derived to synthetic KA, which has introduced a potential source of variability to the implementation of the IHK model. Here, we evaluated injection parameters for synthetic KA, with the goal of identifying conditions that reliably produce spontaneous seizures while minimizing mortality. We found that intrahippocampal injection of 200nL of 5mM synthetic KA resulted in low mortality compared to 50-100nL of 20mM synthetic KA (a dosing range commonly used with naturally derived KA), while robustly inducing TLE-like hippocampal sclerosis and recurrent spontaneous electroclinical seizures. We further demonstrated high inter-animal variability in both seizure frequency and temporal clustering of seizures across animals receiving either injection protocol (200nL of 5mM or 50nL of 20mM). Together, these findings provide a framework for implementing the IHK model with synthetic KA and support its continued use to advance our understanding of the cellular and network mechanisms underlying temporal lobe epilepsy.
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BibTeX
@misc{grillo2026robust,
title = {{Robust Induction of Spontaneous Recurrent Seizures and Hippocampal Sclerosis with Synthetic Kainic Acid in the Intrahippocampal Kainate Model}},
author = {A. R. Grillo and P. O'Gorman and M. Krummradt and M. Kenny and K. J. Staley and K. P. Lillis and L. A. Lau},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.754069},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754069v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Robust Induction of Spontaneous Recurrent Seizures and Hippocampal Sclerosis with Synthetic Kainic Acid in the Intrahippocampal Kainate Model
AU - A. R. Grillo
AU - P. O'Gorman
AU - M. Krummradt
AU - M. Kenny
AU - K. J. Staley
AU - K. P. Lillis
AU - L. A. Lau
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.754069
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.754069v1
AB - Intrahippocampal kainate (IHK) is a well-established mouse model of temporal lobe epilepsy, in which focal hippocampal injection of kainic acid induces excitotoxic injury followed by the development of chronic spontaneous seizures. Commercial sources of kainic acid (KA) have increasingly transitioned from naturally derived to synthetic KA, which has introduced a potential source of variability to the implementation of the IHK model. Here, we evaluated injection parameters for synthetic KA, with the goal of identifying conditions that reliably produce spontaneous seizures while minimizing mortality. We found that intrahippocampal injection of 200nL of 5mM synthetic KA resulted in low mortality compared to 50-100nL of 20mM synthetic KA (a dosing range commonly used with naturally derived KA), while robustly inducing TLE-like hippocampal sclerosis and recurrent spontaneous electroclinical seizures. We further demonstrated high inter-animal variability in both seizure frequency and temporal clustering of seizures across animals receiving either injection protocol (200nL of 5mM or 50nL of 20mM). Together, these findings provide a framework for implementing the IHK model with synthetic KA and support its continued use to advance our understanding of the cellular and network mechanisms underlying temporal lobe epilepsy.
ER -