Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis

EBioMedicine
Hiroki KitauraAkiyoshi Kakita

Abstract

Mesial temporal lobe epilepsy (MTLE) is the most 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 epileptiform activities 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 subiculum affected by HS. Stimulation of mossy 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 subiculum and dentate gyrus could be responsible for epileptogenesis in patients with MTLE.

Citations

Jan 29, 2020·Journal of Veterinary Internal Medicine·Adriana KaczmarskaRodrigo Gutierrez-Quintana
Dec 19, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·D Cunha-ReisP Correia-de-Sá
Jan 12, 2021·Frontiers in Neurology·Masato KinboshiYukihiro Ohno
Apr 13, 2021·Frontiers in Neurology·Paula Agudelo ValenciaUNKNOWN RESPect Database Study Group
Aug 1, 2021·Epilepsy Research·Hiroki KitauraAkiyoshi Kakita
Oct 30, 2021·Journal of Neuroscience Research·Enes AkyuzYam Nath Paudel
Sep 12, 2020·CNS & Neurological Disorders Drug Targets·Shareen SinghAshish Kumar Rehni

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Methods Mentioned

BETA
surgical resection
Fluorescence Imaging
confocal microscopy

Software Mentioned

MATLAB

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