A Study Of NOS Expression In Rats After Kainic Acid-evoked Seizures And Topiramate Treatment

Objective To study the acute and chronic behavioral and electroencephalogram change of a temporal lobe epilepsy(TLE)rat model induced by kainic aicd(KA)and the change by treating with topiramate;and study the spatio-temporal expressions of nNOS,iNOS and eNOS in KA induced rat;then explore the effect of nNOS,iNOS and eNOS and the new antiepileptic mechanism of topiramate.Methods Adult SD rats were used to made a model of TLE by injecting KA to induce epilepticus status.The SD rats were divided into three groups:(1)normal control group; (2)KA group:TLE induced by KA without treatment of topiramate;(3) KA+TPM group:TLE induced by KA with treatment of topiramate.Then each groups were divided into five groups at 1d,1w,2w,3w,4w.Behavioral changes were observed;electrophysiological change were studied by Electroencephalography;and the expressions of nNOS,iNOS and eNOS were investigated with immunohistochemical method.Results(1) Observation of the praxiology:seizure could not been observed in normal control group.Epileptic states were appeared in 76.6%of KA group and chronic spontaneous seizures were appeared in most rats of KA group. Epileptic states were appeared in 21.7%of KA+TPM group and only 24.1%of them appeared chronic spontaneous seizures.The death rate was lower in KA+TPM group compared with that in the KA group.(2)EEG: poly-spik waves,sharp waves,sharp-low complexes and spik waves were observed at KA-evoked seizure rats.(3)Expression of NOS:slight expressions of nNOS,iNOS and eNOS were observed in normal control group.In KA group,nNOS increased in CA1,CA2,CA3 and temporal lobe at acute stage.nNOS also increased in CA2,CA3 and temporal at chronic phase,iNOS increased in all regions at acute stage,iNOS also increased in dentate gyrus and thalamencephal at chronic phase,eNOS increased in CA1, CA2 and dentate gyrus at acute stage,but eNOS was low in CA3,increased to a high level in all regions at chronic phase.In KA+TPM group,nNOS decreased in CA1,CA2,CA3 and temporal lobe,especially at 1d,nNOS also decreased in CA2,CA3 and temporal lobe compare with KA group,iNOS decreased in CA1,CA3,DG and thalamencephal at 1d,also decreased in DG at chronic phase compare with KA group,eNOS decreased in all regions at different time compare with KA group,eNOS was low in CA3 at 1d compare with normal control group.Conclusions The study of praxiology and,EEG suggested that KA intraventriculatal injection could be used to induce TEL of SD rats.The therapy of TPM could obviously lessen the level of the KA-induced seizure.Different subtypes of NOS in SD rats induced by KA were different at different time and different area.The therapy of TPM could obviously reduce expressions of nNOS,iNOS,eNOS.TPM may reduce the activity of NOS and play an anticonvulsant effect.