A cynomolgus monkey model of temporal lobe epilepsy

Abstract

Temporal lobe epilepsy (TLE) with hippocampal sclerosis is the most common type of drug-resistant epilepsy. Non-human primates are attractive models for studying the pathogenic mechanisms of TLE, with the goal of developing new drugs and interventions. In this study, we developed and tested a Cynomolgus monkey (Macaca fascicularis) model of TLE. A total of 5 Cynomolgus monkeys received3–4 weekly unilateral hippocampal injections of kainic acid (KA) to induce repetitive acute seizures. Animals were monitored via video and electroencephalography (EEG) to assess KA-induced acute seizures and subsequent spontaneous recurrent epileptiform discharges (SREDs). During acute seizures, EEG recording showed bursts of generalized spike discharges arising from the temporal lobe ipsilateral to the KA injection. Three months later, we detected abundant interictal epileptiform discharges (IEDs) during pentobarbital induced anesthesia. Furthermore, two monkeys exhibited synchronized epileptiform discharges accompanied by symptoms mimicking absence seizures. No obvious convulsive symptoms were observed in any monkeys. Overall, our data indicate successful development of a Cynomolgus monkey model of TLE via unilateral hippocampal injection of KA.