Early and Bi-hemispheric seizure onset in a rat glioblastoma Multiforme model

Abstract

GBM is the most life-threatening neurological disease with annual incidence of ∼ 5 cases per 100,000 people and a median survival of less than 15 months. Seizures are the first clinical symptoms in 40%-45% of patients with GBM and its epileptogenic mechanisms are poorly understood, largely due to the challenge to develop a clinically-relevant animal model and the unknown latent period. In this study, we used continuous video-EEG monitoring to detect the earliest interictal and ictal events in a CRISPR- IUE GBM rat model that shares pathological and clinical features with those observed in human patients. To our best knowledge, we showed for the first time that interictal epileptiform discharges emerged during early postnatal weeks and the first ictal event occurred during the fourth postnatal week. We also showed GBM animals showed independent bi-hemispheric epileptogenic events, suggesting a widespread circuitry dysregulation. Together, our work identified the temporal- and spatial frame of epileptogenic network in a highly clinically-relevant GBM animal model, paving ways for mechanistic studies at molecular, cellular and circuitry levels.