Implementing a bioassay to screen molecules for antiepileptogenic activity: chronic pilocarpine versus subdudral haematoma models.
BACKGROUND
There is a need to discover novel chemical compounds that will inhibit the pathological process of epileptogenesis (i.e. agents that will prevent the long-term formation of an active seizure focus following a brain insult). The goal of this paper is to identify a bioassay of value in drug design when screening new chemical entities as putative antiepileptogenic agents.


METHODS
We focused on two models: the pilocarpine chronic seizure model of spontaneous recurrent seizures (SRSs) and a chronic subdural haematoma model of SRSs. Both models were evaluated using more than 20 Sprague-Dawley rats for each model.


RESULTS
In the pilocarpine-induced model of SRSs, 80% of animals went on to develop SRSs when the dose of pilocarpine was 380 mg/kg i.p. In 50 animals that developed SRSs, the average number of seizures per 15 days of observation was 3.8 seizures with a range of 2-23 seizures per 15-day period. The chronic subdural model was inefficient in producing SRSs.


CONCLUSIONS
A pilocarpine-induced SRS model of epilepsy affords a reliable model of epileptogenesis suitable for evaluating new chemical entities as putative antiepileptogenics.
Lyon
Angela
A
Department of Chemistry, Queen's University, Kingston, Ont., Canada K7L 3N6.
Marone
Sandra
S
Wainman
Dan
D
Weaver
Donald F
DF
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D006408:Hematoma, Subdural / Q000150:complications* / Q000453:epidemiology / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D010862:Pilocarpine / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D014743:Videotape Recording
D018721:Muscarinic Agonists; D010862:Pilocarpine