Large Animal Epilepsy Model Platform: Kainic Acid Porcine Model of Mesial Temporal Lobe Epilepsy

Translational animal models that can accommodate human-scale implantable devices are essential for advancing chronic brain stimulation and sensing applications. This study establishes a kainic acid (KA)-induced porcine model of mesial temporal lobe epilepsy (mTLE) using a neurotechnology platform integrating clinical imaging, stereotactic surgery, and a fully implantable device for chronic monitoring. In six KA-treated and one saline-control pig bilateral hippocampus (HPC) and anterior thalamus (ANT) local field potentials were monitored using an implantable device, along with synchronized video recordings. Histology was performed to assess neuronal injury and hippocampal reorganization. Intra-hippocampal KA infusion induced acute status epilepticus (6/6 pigs). Surviving KA-treated pigs (4/6) were monitored for a total of 386 days with spontaneous seizures occurring in three subjects. A total of 2,733 hippocampal seizures were recorded with a seizure duration of 27.16{+/-}17.62 seconds. All subjects exhibited bilateral interictal epileptiform discharges, predominantly in the lesioned hemisphere (p <0.0001). Histological analysis revealed cytoarchitectural disorganization consistent with hippocampal injury. This porcine model recapitulates many of the electrophysiological and structural hallmarks of human mTLE. The platform provides a powerful translational bridge for developing novel sensing and stimulating neuromodulation strategies in freely behaving large animals using human-scale implantable devices.