A new, non-pharmacologic 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 describes a non-pharmacologic model of generalized convulsive SE in rat. Pulsed trains of suprathreshold electric current, were administered bilaterally to either of four rostral forebrain sites: orbital cortex, medial precentral cortex, deep prepiriform cortex, or rostral caudate-putamen (n = 8 per site). This induction method resulted in 30/32 animals attaining limb-clonic convulsive SE within a mean of 30-35 min for each forebrain site, with no differences between sites. Subsequent SE proceeded without further interventions, permitting observation of the natural course of progression. A stereotyped behavioral/electrographic sequence occurred, characterized by devolution. Behaviorally, animals progressed from predominantly limb clonus to head clonus, then to subtle twitching, and finally to electrical SE before cessation of spikes. The corresponding electrographic progression was from fast and slow spiking to periodic epileptiform discharges (PEDs). In 20 animals surviving to 48 h, pathologic damage affected mainly limbic sites; damage was related to total convulsive time rather than to clonic activity. High-dose phenobarbital but not phenytoin suppressed SE when given during orbital cortex-induced limb-clonic SE. These findings are compatible with human observations and indicate that this model will enable investigations of generalized SE mechanisms and evaluation of new therapeutic agents for refractory SE.
Handforth
A
A
Department of Veterans Affairs Medical Center, West Los Angeles, CA.
Treiman
D M
DM
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects*; D004830:Epilepsy, Tonic-Clonic / Q000209:etiology / Q000473:pathology; D007262:Infusions, Intravenous; D010634:Phenobarbital / Q000627:therapeutic use*; D010672:Phenytoin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology
D010672:Phenytoin; D010634:Phenobarbital