A NEW, NONPHARMACOLOGICAL MODEL OF CONVULSIVE STATUS EPILEPTICUS INDUCED BY ELECTRICAL-STIMULATION - BEHAVIORAL ELECTROENCEPHALOGRAPHIC OBSERVATIONS AND RESPONSE TO PHENYTOIN AND PHENOBARBITAL/

Much remains to be learned about mechanisms underlying entry into, and temporal progression of, status epilepticus (SE). This report describ es a non-pharmacologic model of generalized convulsive SE in rat. Puls ed trains of suprathreshold electric current were administered bilater ally to either of four rostral forebrain sites: orbital cortex, medial precentral cortex, deep prepiriform cortex, or rostral caudate-putame n (n=8 per site). This induction method resulted in 30/32 animals atta ining limb-clonic convulsive SE within a mean of 30-35 min for each fo rebrain site, with no differences between sites. Subsequent SE proceed ed without further interventions, permitting observation of the natura l course of progression. A stereotyped behavioral/electrographic seque nce occurred, characterized by devolution. Behaviorally, animals progr essed from predominantly limb clonus to head clonus, then to subtle tw itching, and finally to electrical SE before cessation of spikes. The corresponding electrographic progression was from fast and slow spikin g to periodic epileptiform discharges (PEDs). In 20 animals surviving to 48 h, pathologic damage affected mainly limbic sites; damage was re lated to total convulsive time rather than to clonic activity. High-do se phenobarbital but not phenytoin suppressed SE when given during orb ital cortex-induced limb-clonic SE. These findings are compatible with human observations and indicate that this model will enable investiga tions of generalized SE mechanisms and evaluation of new therapeutic a gents for refractory SE.