Publication
Title
Changes in hippocampal density during limbic epileptogenesis : relationship to cell loss and mossy fibre sprouting
Author
Abstract
Reduced GABAA/central benzodiazepine receptor (GABAA/cBZR) density, mossy fibre sprouting (MFS) and hippocampal cell loss are well described pathological features of human temporal lobe epilepsy (TLE), and animal models thereof. However, the temporal relationship of their development, and their roles in the emergence of the epilepsy, are uncertain. This was investigated in the kainic acid (KA)-induced post-status epilepticus (SE) model of TLE. Male Wistar rats (7 weeks, n = 53) were randomised into control and KA groups. At 24 h, 2, 4 or 6 weeks sham and KA post-SE animals were euthanised, brains extracted and GABAA/cBZR density, neuronal loss and MFS measured in hippocampal sub-regions. GABAA/cBZR density (Bmax) was measured by saturation-binding analysis using [3H]-flumazenil. At 24 h post-SE GABAA/cBZR density was increased in almost all hippocampal subregions, but was decreased at the later time points with the exception of the dentate gyrus. There was significant neuronal loss in the CA3 SPc region (−24±9.3%, p<0.05) at 24h, which remained stable at the later time points associated with an elevated GABAA/cBZR density per surviving neuron at 24h post-SE (+56.4%; p<0.05) which returned to control levels by 6 weeks post-SE. MFS in the dentate gyrus progressively increased over the 6 weeks following SE (+ 70.6% at 6 weeks), at which time there was a significant inverse relationship with GABAA/cBZR binding (r2 = 0.87; p = 0.02). The temporal evolution of GABAA/cBZR density changes post-KA-induced SE, and the relationship with decreases in hippocampal pyramidal cell numbers and MFS, may point to a key role for these changes in the pathogenesis of acquired limbic epileptogenesis.
Language
English
Source (journal)
Neurobiology of disease. - San Diego, Calif.
Publication
San Diego, Calif. : 2011
ISSN
0969-9961
Volume/pages
41:2(2011), p. 227-236
ISI
000286154300001
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 16.02.2011
Last edited 04.11.2017
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