The vital dye Evans blue mimics limbic seizures induced by kainate or pilocarpine.
Evans blue dye, given i.c.v. in rats in a dose of 208 nmol, causes electrical and behavioural seizures which resemble those induced by the glutamate analogue, kainate, or by electrical kindling of the amygdala. Chicago sky blue, 201 nmol i.c.v., produces similar seizures. The principal elements of the seizures are wet-rat-shakes, facial and forelimb clonus, rearing and spike-and-waves in the EEG. A non-NMDA receptor antagonist, GYKI 52466 and a benzodiazepine, diazepam, significantly delay the onset to the occurrence of the first forelimb clonus. The cholinergic antagonist, scopolamine, significantly reduces the delay to onset of first facial clonus. The competitive NMDA receptor antagonist, D-CPPene, the non-specific dopamine antagonist, haloperidol, and the purinergic agonist, 2-chloroadenosine, have no effect on the measured parameters. During the induction of seizures by Evans blue, the average extracellular glutamate concentration in hippocampus or cortex does not increase statistically significantly in comparison to pre-seizure values. Histological examination of limbic areas indicates that the moderate to severe Evans blue-induced cell damage is similar to that seen after limbic seizures induced by pilocarpine and in the hippocampus is partially preventable by D-CPPene but not by diazepam or GYKI 52466. It is proposed that Evans blue-induced seizures may be useful as a new model for studying the mechanisms of intractable epilepsy of the complex partial seizure type.
Dürmüller
N
N
Department of Neurology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK.
Graham
J L
JL
Sowinski
P
P
Meldrum
B S
BS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004396:Coloring Agents / Q000494:pharmacology; D004569:Electroencephalography; D005070:Evans Blue / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D007608:Kainic Acid; D008032:Limbic System / Q000503:physiopathology*; D008297:Male; D017551:Microdialysis; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
D004396:Coloring Agents; D018690:Excitatory Amino Acid Agonists; D010862:Pilocarpine; D018698:Glutamic Acid; D005070:Evans Blue; D007608:Kainic Acid