title: Antiepileptogenic effects of the selective COX-2 inhibitor etoricoxib, on the development of spontaneous absence seizures in WAG/Rij rats.
abstract: Different data suggest the involvement of specific inflammatory pathways in the pathogenesis of epilepsy. Cyclooxygenase (COX), which catalyses the production of pro-inflammatory prostaglandins, may play a significant role in seizure-induced neuroinflammation and neuronal hyperexcitability. COX-2 is constitutively expressed in the brain and also increased during/after seizures. COX-2 inhibitors may thus attenuate inflammation associated with brain disorders. We studied whether early long-term treatment (17 consecutive weeks starting from 45 days postnatal age) with the non-steroidal anti-inflammatory drug etoricoxib (10 mg/kg/day per os), a selective COX-2 inhibitor, was able to prevent/reduce the development of absence seizures in WAG/Rij rats, a recognized animal model of absence epilepsy and epileptogenesis. Drug effects on the incidence, duration and properties of absence seizure spike-wave discharges (SWDs) were measured both 1 and 5 months after treatment withdrawal; furthermore, the acute effects of etoricoxib on SWDs in 6-month-old WAG/Rij rats were measured. Early long-term treatment (ELTT) with etoricoxib led to an ∼40% long-lasting (5 months) reduction in the development of spontaneous absence seizures in adult WAG/Rij rats thus exhibiting antiepileptogenic effects. Acutely administered etoricoxib (10 and 20mg/kg i.p.) also had anti-absence properties, significantly reducing the number and duration of SWDs by ∼50%. These results confirm the antiepileptogenic effects of COX-2 inhibitors and suggest the possible role of COX-2, prostaglandin synthesis and consequent neuroinflammation in the epileptogenic process underlying the development of absence seizures in WAG/Rij rats.
authors.affiliation: University of Catanzaro, School of Medicine, Department of Science of Health, Catanzaro, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.affiliation: University of Catanzaro, School of Medicine, Department of Science of Health, Catanzaro, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Leo
authors.affiliation: National Council of Research (CNR), Institute of Neurological Science, Catanzaro, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Marra
authors.affiliation: University of Catanzaro, School of Medicine, Department of Science of Health, Catanzaro, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.affiliation: University of Catanzaro, School of Medicine, Department of Science of Health, Catanzaro, Italy. Electronic address: erusso@unicz.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D000077613:Etoricoxib; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D052246:Cyclooxygenase 2 Inhibitors; D011725:Pyridines; D013450:Sulfones; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000077613:Etoricoxib
keywords: Absence epileptogenesis; Cyclooxygenase (COX); Etoricoxib; Neuroinflammation; Spike-wave discharges (SWDs); WAG/Rij rats