Changes in hippocampal GABAA /cBZR density during limbic epileptogenesis: Relationship to cell loss and mossy fibre sprouting

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 [3 H]-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