Abstracts

Reduced GABA[sub]A[/sub]/central benzodiazepine receptor (GABA[sub]A[/sub]/cBZR) expression, mossy fibre sprouting (MFS) and hippocampal sclerosis are common pathological changes seen in both human and animal models of temporal lobe epilepsy (TLE). This study was designed to investigate immediate (24 hours) and long-term changes (2, 4 and 6 weeks) in GABA[sub]A[/sub]/cBZR expression, neuronal loss and MFS in the hippocampus in the kainic acid (KA)-induced [italic]status epilepticus[/italic] (SE) model of TLE., Age-matched non-epileptic control male rats were randomized into control and KA groups (at least n=6/group). MFS and GABA[sub]A[/sub]/cBZR expression, neuronal loss and MFS were measured in hippocampal subregions, dentate gyrus (DG), CA3 and CA1 in both the control and epilepsy groups. GABA[sub]A[/sub]/cBZR expression (Bmax value) was measured by saturation-binding analysis using [³H]-Flumazenil, a cBZR antagonist. Stereological counting was performed for cell counting and volume analysis of the CA3 SPc subregion of the hippocampus. MFS into the dentate molecular layer was quantified from Timm-stained brain slices., At 24 hours post-SE, Bmax was significantly increased compared to controls in the whole hippocampus (+29.4%[plusmn]5.7; p[lt]0.001) and parietal cortex (Par Ctx) (+30.6%[plusmn] 12.8; p[lt]0.05) as well as in all subregions of the DG, CA1, and CA3 with the exception of CA3 SPc (Repeated measure ANOVA, p[lt]0.02). Calculated from absolute values, no changes in receptor expression were seen over 2-6 weeks. There was no difference in MFS 24 hours post-SE compared with controls but MFS increased in the dentate molecular layer at 2 weeks post SE (20% above control; p[lt]0.05) and showed a progressive increase over time reaching 70% above controls (p[lt]0.001) at 6 weeks. At 24 hours, statistically significant neuronal loss occurred (-24[plusmn]9.3%) in the CA3 SPc region (control=6, KA group=6, p[lt]0.05) associated with a significant increase in GABA[sub]A[/sub]/cBZR expression per surviving neuron. No recovery of neurons was apparent through to the end of 6 weeks post-SE., Changes in GABA[sub]A[/sub]/cBZR expression, cell loss and synaptic reorganization occur during epileptogenesis and may influence the severity of spontaneous recurrent seizures (SRS). Elevated receptor expression observed early after [italic]status epilepticus[/italic] (within 24 hours) may be a protective response by the brain to dampen excitability and increase resistance to future seizures. MFS, a form of neuronal reorganization, is a prominent feature in the KA model of TLE progressively increasing during the latent epileptogenic period up to onset of SRS. GABA[sub]A[/sub]/cBZR expression and MFS were not correlated until 6 weeks implying that MFS may affect seizure activity in late stages of epilepsy onset.,