Abstracts

RATIONALE: Synaptic reorganization of the dentate granule cells (GC) may be important in the pathogenesis of temporal lobe epilepsy (TLE). However, recent work showed that the protein synthesis inhibitor cyclohexamide (CHX) blocked mossy fiber sprouting but not chronic seizures in the pilocarpine (PILO) model of TLE (Longo and Mello, Neurosci. Lett. 226 (1997) 163-166). METHODS: We reexamined the effect of CHX in PILO-treated rats on behavioral seizures, mossy fiber sprouting in the inner molecular layer (IML), epileptiform activity in the granule cell layer (GCL) and EPSCs in GCs. Three groups were studied: 1) CHX injection (1 mg/kg) prior to PILO treatment (320 mg/kg), 2) PILO only and 3) saline. RESULTS: Latent period and seizure rate were not significantly different between rats pretreated with CHX and rats treated with PILO only. The amount of Timm stain in the IML was similar between these two groups (p>0.05). In bicuculline (30 ?M) and elevated [K+]o (6 mM), hilar stimulation evoked epileptiform bursts in the GCL in both PILO- and CHX-PILO-treated rats. Burst duration was strongly correlated with the amount of Timm stain (r2=0.7), independent of treatment. The EPSC amplitude was significantly larger in GCs from PILO- and CHX-PILO-treated rats than in GCs from controls, but not different between each other (p<0.001 and p>0.1 respectively). CONCLUSIONS: These results suggest that in the PILO model of TLE, pretreatment with CHX 1) does not change seizure rate, 2) does not prevent mossy fiber sprouting in the IML, and 3) does not change the duration of epileptiform bursts in the GCL or the increase in EPSC amplitude in GCs. (Supported by NS16683 to FED and NS10643 to PAW)