Effects of Topiramate on neuronal ultrastructure and bcl-2 expression in hippocampus of epileptic rats

Objective To observe the effects of Topiramate (TPM) on the neuronal ultrastructure and bcl-2 expression in hippocampus of epileptic rats, in order to explore possible mechanisms of neuroprotective effect of Topiramate.Methods Forty-two SD rats were randomly assigned into three groups: blank control group (n=6), kanic acid (KA) group and TPM group (n=18 each). A model of status epilepticus (SE) was induced by intraperitoneal injection of KA (10 mg/kg). Before preparation of the model, the TPM group received intragastric administration of TPM (18 mg/kg daily) for 15 days; normal saline of equal volume was administered to the KA group. The blank control group did not received any treatment. 6, 24 and 48 hrs after SE, the rats were sacrificed and the hippocampus were removed. The neuronal ultrastructure was observed under an electron microscope, and immunohistochemical staining was used to examine the protein level of bcl-2.Results The neurons of the KA group showed characteristics of apoptosis. The neuronal ultrastructures of the rats from the TPM group were nearly normal, nucleole margination and increment of both Golgi body and lysosome were observed. Few apoptotic neurons were noted in the TPM group. In the KA group, the expression of bcl-2 increased 6 hrs after SE (compared with the blank control group, P0.05), but began to decrease at 24 hrs, and only a weak expression was detected at 48 hrs. The expression of bcl-2 in the TPM group increased at 6 hrs, peaked at 24 hrs and remained a higher level until 48 hrs.Conclusions Pretreatment with TPM could reduce neuronal injury in epileptic rats. The neuroprotection might be related to the up-regulation of bcl-2 expression.