A steroid derivative (RU 5135) exhibits epileptogenicity in the presence of deficient blood-brain barrier.
A hypothesis was tested that epileptic spiking, induced by systemic administration of a steroid derivative (RU 5135), may be associated with surgery-related cortical damage rather than epileptogenicity of the agent. Cumulative doses of the drug were given to rats and rabbits. The lasting quasi-periodic seizure discharges were always seen initially only under an epicortical electrode implant. Brain damage in inflicted by such an electrode was confirmed anatomically (by assessing the area of lesion) and noninvasively (by showing contrast-induced enhancement of CT brain images in the hemisphere homolateral to epicortical electrodes). The threshold of epileptic spiking varied inversely with the area of cortical damage inflicted by the electrode. In a number of cases no spiking was obtained from the hemisphere with nonpenetrating (intraosteal) electrodes. We caution that a breach of the BBB caused by conventional surgery in rodents can make a benign drug appear as excessively toxic thereby discrediting potentially useful compounds.
Myslobodsky
M S
MS
Department of Psychology Tel Aviv University, Jerusalem, Israel.
Mintz
M
M
Tarrasch
R
R
Bar-Ziv
J
J
D000731:Androstanes / Q000494:pharmacology*; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D001522:Behavior, Animal; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology; D002682:Chinchilla; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced*; D005260:Female; D008297:Male; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014057:Tomography, X-Ray Computed
D000731:Androstanes; D001378:Azasteroids; C032061:RU 5135