Recurrent spontaneous hippocampal seizures in the rat as a chronic sequela to limbic status epilepticus.
A period of continuous hippocampal stimulation (CHS) establishes an acute condition of self-sustaining limbic status epilepticus (SSLSE) which is followed by chronic neuropathological changes reminiscent of hippocampal sclerosis encountered in epileptic patients. In the chronic (greater than or equal to 1 month) condition following CHS-induced SSLSE, extended electrographic monitoring in the hippocampus revealed spontaneous recurrent paroxysmal discharges. All 6 animals studied had persistent interictal spiking; 3 had multiple fully developed electrographic seizures. There was a marked diminution of paired pulse inhibition, demonstrated by a protocol known to reflect the potency of inhibition mediated by GABAA receptors. Hippocampal slices from animals that had previously experienced CHS-induced SSLSE demonstrated an increased excitability relative to slices from control animals as evidenced by epileptiform bursting in increased extracellular potassium ([K+]0) and decreased extracellular calcium ([Ca2+]0). These studies establish that CHS-induced SSLSE in rats provides an experimental model with recurrent spontaneous hippocampal seizures. Based on electrophysiological data we suggest that a decrease in GABA-mediated inhibition and/or altered sensitivity to extracellular ions may play roles in the development of such seizures.
Lothman
E W
EW
Department of Neurology, University of Virginia School of Medicine, Charlottesville 22908.
Bertram
E H
EH
Kapur
J
J
Stringer
J L
JL
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D006624:Hippocampus / Q000503:physiopathology*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D012008:Recurrence; D012640:Seizures / Q000503:physiopathology*; D013226:Status Epilepticus / Q000503:physiopathology*
D009118:Muscimol