title: Increased permeability of the blood-brain barrier following administration of glyceryl trinitrate in common carp (Cyprinus carpio L.).
abstract: Nitric oxide (NO) has been implicated in the pathogenesis of migraine and treatment with its exogenous donor glyceryl trinitrate (GTN) represents widely accepted experimental "migraine model". In this study, glyceryl trinitrate was administered intraperitoneally to carps, serum nitrite and nitrate levels were determined, permeability of blood-brain barrier was investigated, and histological changes of brain tissue were analyzed. Serum nitrite and nitrate levels displayed characteristic biphasic pattern with moderate initial increase and maximal terminal increase, suggesting the GTN-induced endogenous NO synthesis. Increased permeability of the blood-brain barrier in GTN-treated animals was determined based on Evans blue capillary leakage into the brain tissue. Histological analysis revealed changes consistent with vasodilatation and oedema. Our study strongly supports the importance of the NO role in the pathogenesis of migraine attacks and increase in blood-brain barrier permeability during the attack. The study has also provided evidence that this mechanism of action is conserved to the lower vertebrate.
authors.affiliation: Department of Neurology, General Hospital Zabok, Zabok, Croatia. sanja.drca@kr.htnet.hr
authors.forename: Sanja
authors.initials: S
authors.lastname: Kovacić
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Petrinec
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Matasin
authors.forename: Emil
authors.initials: E
authors.lastname: Gjurcević
authors.forename: Goran
authors.initials: G
authors.lastname: Ivkić
authors.forename: Arijana
authors.initials: A
authors.lastname: Lovreneić-Huzjan
authors.forename: Maja
authors.initials: M
authors.lastname: Segvić-Klarić
authors.forename: Lada
authors.initials: L
authors.lastname: Rumora
authors.forename: Stjepan
authors.initials: S
authors.lastname: Pepeljnjak
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002347:Carps; D002463:Cell Membrane Permeability / Q000187:drug effects*; D008881:Migraine Disorders / Q000209:etiology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D005996:Nitroglycerin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin