A rat model of repeated seizures induced by pentylenetetrazol at different maturational stages and the role of NF-κB in the pathogenesis of epilepsy

AIM: To observe histopathologic changes and NF-κB expression in hippocampus in neonatal and matural rats after repeated seizures, and to explore the role of NF-κB in the pathogenesis of epilepsy in premature brain of rats. METHODS: Neonatal rats and mature rats were divided into 2 experimental groups at 10 days and 60 days after birth (P10 and P60). Convulsions were induced by repeated injection of pentylenetetrazol (PTZ) intraperitoneally for first 5 days. The animals in control group were injected with NS at the same volume in the same conditions. The neurons in CA1, CA3, dentate granule (DG), as well as in hilar were counted by thionin staining, in order to observe the profile of the necrosis and apoptosis. NF-κB expression was examined by immunohistochemistry assay. Timm's method of silver sulfide staining was adopted to observe the mossy fiber sprouting. RESULTS: (1) In immature rats (10 days old), neurons in CA1, CA3 and hilar demonstrated no differences from controls, whereas adult rats (P60) had a significant decrease in number of neurons in CA1 and CA3 (8.22±1.88, 5.62±1.68 vs 6.31±1.50, 3.62±1.40). In adult rats, neurons in dentate granule showed no differences with controls, whereas immature rats with daily seizures had a significant increase (23.25±3.06 vs 16.25±1.58). (2) There was prominent sprouting in the CA3 stratum pyramidal layer in all experimental rats after 5 daily seizures, regardless of the age. However, the degree of sprouting was significantly different between the two experimental groups (3.25±1.03 vs 1.50±0.92, P0.05). (3) NF-κB was highly expressed in CA3, CA1 and DG after 24 hours by PTZ-kindling, whereas it was little expressed in control group. NF-κB expression was higher in P10 experimental rats than that in P60 rats. CONCLUSION: No cell loss was observed in hippocampus in neonatal rats after recurrent kindling. The high expression of NF-κB may be one of the important molecular mechanisms underlying the special resistance of the neurons in premature brain to the epileptic cerebral lesions.