Synergism between topiramate and budipine in refractory status epilepticus in the rat.

Abstract:

PURPOSE:To evaluate the antiepileptic and neuroprotective properties of topiramate (TPM) alone and with coadministration of the N-methyl-D-aspartate (NMDA)-receptor antagonist budipine in a rat model of refractory status epilepticus. METHODS:Male Sprague-Dawley rats had electrodes implanted into the perforant path and dentate granule cell layer of the hippocampus under halothane anesthesia. Approximately 1 week after surgery, the perforant path of each animal was electrically stimulated for 2 h to induce self-sustaining status epilepticus. Successfully stimulated rats were given intraperitoneally vehicle (n = 6), TPM (20-320 mg/kg; n = 28), budipine (10 mg/kg; n = 5), or budipine (10 mg/kg) and TPM (80 mg/kg; n = 6) 10 min after the end of the stimulation and monitored behaviorally and electroencephalographically for a further 3 h. The animals were killed 14 days later, and histopathology was assessed. RESULTS:Neither budipine alone nor TPM at any dose terminated status epilepticus. Despite this, TPM resulted in various degrees of neuroprotection at doses between 40 and 320 mg/kg. Coadministration of budipine with TPM terminated the status epilepticus in all rats. This combination also significantly improved the behavioral profile and prevented status-induced cell death compared with control. CONCLUSIONS:Budipine and TPM are an effective drug combination in stopping self-sustained status epilepticus, and TPM alone was neuroprotective, despite the continuation of seizure activity.

journal_name

Epilepsia

journal_title

Epilepsia

authors

Fisher A,Wang X,Cock HR,Thom M,Patsalos PN,Walker MC

doi

10.1111/j.0013-9580.2004.26404.x

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

1300-7

issue

11

eissn

0013-9580

issn

1528-1167

pii

EPI26404

journal_volume

45

pub_type

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