期刊
NEUROBIOLOGY OF DISEASE
卷 41, 期 2, 页码 227-236出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2010.08.021
关键词
Epileptogenesis; Temporal lobe epilepsy; gamma-amino butyric acid type A/central; benzodiazepine receptor; Hippocampus; Receptor density; Epilepsy seizures
资金
- Cooperative Research Centre for Biomedical Imaging Development (CRC-BID), Australia
Reduced GABA(A)/central benzodiazepine receptor (GABA(A)/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 GABA(A)/cBZR density, neuronal loss and MFS measured in hippocampal sub-regions. GABA(A)/cBZR density (B-max) was measured by saturation-binding analysis using [H-3]-flumazenil. At 24 h post-SE GABA(A)/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 GABA(A)/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 GABA(A)/cBZR binding (r(2) = 0.87; p= 0.02). The temporal evolution of GABA(A)/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. (C) 2010 Elsevier Inc. All rights reserved.
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