Flupirtine’s anticonvulsant role +/- celecoxib versus diazepam on induced generalized seizures and status epilepticus in mice
Epilepsy represents a personal and major community burden because about one-third of epileptic patients remain resistant to medical treatment. Flupirtine, as a potassium channel opener, can be a rational template for the treatment of epilepsy. To investigate flupirtine +/- celecoxib versus diazepam anticonvulsant role on induced epilepsy in mice. Generalized seizures and status epilepticus were induced by pentylenetetrazole and lithium/pilocarpine, respectively. The latency period to 1st seizure was calculated. A modified racine’s scale was used to characterize behavioral and electrographic seizures. Brain GABA and IL-6 levels were measured. Cresyl violet stain and Glial fibrillary acidic protein (GFAP) immunostain were used to assess hippocampal irreversible neuronal damage and gliosis. Diazepam and flupirtine prolonged latency periods to 1st seizure, attenuated behavioral seizures, recorded lower grades of electrographic seizures, and guarded against a decline in brain GABA level. The three drugs used attenuated brain IL-6 level, chiefly in the treated groups of the celecoxib. Irreversible neuronal damage and increased GFAP immunoreactivity witnessed in the hippocampus of both seizure models were markedly mitigated, mostly in diazepam/celecoxib and combined therapy. Diazepam, flupirtine and celecoxib possess anticonvulsant, immuno-modulatory and neuroprotective effects. Diazepam is still superior in controlling seizures and EEG changes, while celecoxib is the least effective. Flupirtine showed almost the same results as diazepam in biochemical parameters in addition to better histopathological results, indicating that it is a promising drug that could contribute to the control of seizures.
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