Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis

Mesial temporal lobe epilepsy (MTLE) is themost frequent focal epileptic syndrome in adults, and the majority of seizures originate primarily from the hippocampus. The resected hippocampal tissue often shows severe neuronal loss, a condition referred to as hippocampal sclerosis (HS). In order to understand hippocampal epileptogenesis in MTLE, it seems important to clarify any discrepancies between the clinical and pathological features of affected patients. Here we investigated epileptiformactivities ex vivo using living hippocampal tissue taken from patients with MTLE. Flavoprotein fluorescence imaging and local field potential recordings revealed that epileptiform activities developed from the subiculum. Moreover, physiological and morphological experiments revealed possible impairment of K+ clearance in the subiculumaffected by HS. Stimulation ofmossy fibers induced recurrent trans-synaptic activity in the granule cell layer of the dentate gyrus, suggesting that mossy fiber sprouting in HS also contributes to the epileptogenic mechanism. These results indicate that pathophysiological alterations involving the subiculumand dentate gyrus could be responsible for epileptogenesis in patients with MTLE. (C) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.