Organoids as a model of status epilepticus

Abstract

Status epilepticus (SE) is a neurological emergency that can be studied in animal models, particularly mice. However, these models are labour-intensive and require large numbers of animals, which raises ethical and logistical challenges. Additionally, rodent-based models could lack direct relevance to human physiology. While reduced models offer some insights, they fail to replicate the full complexity of brain connectivity and interactions with other organs. To address this, human forebrain assembloids, formed by both cortical excitatory and subpallial inhibitory neurons, could be an alternative SE model. Assembloids offer a middle ground, enabling high-throughput screening of potential treatments while maintaining relevant human cell biology. This approach could serve as an intermediate step before transitioning to animal models, ultimately reducing the time and number of animals required for SE research. This paper is based on a presentation made at the 9thLondon-Innsbruck Colloquium on Status Epilepticus and Acute Seizures in April 2024.

Keywords: Assembloids; In vitro model; Status epilepticus; Therapeutics; iPSC-derived neurons.