Ictal onset sites and γ‐aminobutyric acidergic neuron loss in epileptic pilocarpine‐treated rats
- 3 April 2020
- Vol. 61 (5), 856-867
- https://doi.org/10.1111/epi.16490
Abstract
Objective The present study tested whether ictal onset sites are regions of more severe interneuron loss in epileptic pilocarpine‐treated rats, a model of human temporal lobe epilepsy. Methods Local field potential recordings were evaluated to identify ictal onset sites. Electrode sites were visualized in Nissl‐stained sections. Adjacent sections were processed with proximity ligation in situ hybridization for glutamic acid decarboxylase 2 (Gad2). Gad2 neuron profile numbers at ictal onset sites were compared to contralateral regions. Other sections were processed with immunocytochemistry for reelin or nitric oxide synthase (NOS), which labeled major subtypes of granule cell layer–associated interneurons. Stereology was used to estimate numbers of reelin and NOS granule cell layer–associated interneurons per hippocampus. Results Ictal onset sites varied between and within rats but were mostly in the ventral hippocampus and were frequently bilateral. There was no conclusive evidence of more severe Gad2 neuron profile loss at sites of earliest seizure activity compared to contralateral regions. Numbers of granule cell layer–associated NOS neurons were reduced in the ventral hippocampus. Significance In epileptic pilocarpine‐treated rats, ictal onset sites were mostly in the ventral hippocampus, where there was loss of granule cell layer–associated NOS interneurons. These findings suggest the hypothesis that loss of granule cell layer–associated NOS interneurons in the ventral hippocampus is a mechanism of temporal lobe epilepsy.Keywords
Funding Information
- NIH/NINDS
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