title: Topiramate reduces blood-brain barrier disruption and inhibits seizure activity in hyperthermia-induced seizures in rats with cortical dysplasia.
abstract: We investigated the effects of topiramate (TPM), a novel broad spectrum anticonvulsant, on seizure severity, survival rate and blood-brain barrier (BBB) integrity during hyperthermic seizures in rats with cortical dysplasia (CD). Offsprings of irradiated mothers were used in this study. To show the functional and morphological alterations in BBB integrity, quantitative analysis of Evans blue (EB) extravasation, immunohistochemistry and electron microscopic assessment of horseradish peroxidase (HRP) permeability were performed. Rats with CD exposed to hyperthermia exhibited seizures with mean Racine's scores of 3.92 ± 1.2. Among the rats with CD pretreated with TPM, 21 of 24 rats showed no sign of seizure activity upon exposure to hyperthermia (p<0.01). The immunoreactivity of occludin, a tight junction protein, remained essentially unaltered in capillaries of hippocampus in all groups. In animals with CD exposed to hyperthermia, the significantly increased p-glycoprotein immunoreactivity in hippocampus (p<0.01) was slightly decreased by TPM pretreatment. Hyperthermic seizures increased BBB permeability to EB in animals with CD, but TPM pretreatment decreased the penetration of the tracer into the brain in these animals (p<0.01). Ultrastructurally frequent vesicles containing HRP reaction products were observed in capillary endothelial cells in cerebral cortex and hippocampus of rats with CD subjected to hyperthermia-induced seizures, and TPM pretreatment prevented the development of HRP reaction products in these animals. The results of this study suggest that TPM inhibits seizure activity and maintains BBB integrity in the course of febrile seizures in the setting of CD.
authors.affiliation: Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Candan
authors.initials: C
authors.lastname: Gürses
authors.forename: Nurcan
authors.initials: N
authors.lastname: Orhan
authors.forename: Bulent
authors.initials: B
authors.lastname: Ahishali
authors.forename: Canan Ugur
authors.initials: CU
authors.lastname: Yilmaz
authors.forename: Gonul
authors.initials: G
authors.lastname: Kemikler
authors.forename: Imdat
authors.initials: I
authors.lastname: Elmas
authors.forename: Aydin
authors.initials: A
authors.lastname: Cevik
authors.forename: Mutlu
authors.initials: M
authors.lastname: Kucuk
authors.forename: Nadir
authors.initials: N
authors.lastname: Arican
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kaya
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005334:Fever; D005632:Fructose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D003294:Seizures, Febrile / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000077236:Topiramate
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose