Increased permeability of the blood-brain barrier following administration of glyceryl trinitrate in common carp (Cyprinus carpio L.)

Kovačić, Sanja and Petrinec, Zdravko and Matašin, Željka and Gjurčević, Emil and Ivkić, Goran and Lovrenčić-Huzjan, Arijana and Šegvić-Klarić, Maja and Rumora, Lada and Pepeljnjak, Stjepan (2008) Increased permeability of the blood-brain barrier following administration of glyceryl trinitrate in common carp (Cyprinus carpio L.). Collegium Antropologicum, 32 (S. 1). pp. 99-103. ISSN 0350-6134

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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.

Abstract in Croatian

Dušik (II) oksid (NO) je impliciran u patogenezi migrene, a tretiranje njegovim egzogenim donorom gliceril trinitratom (GTN), predstavlja općenito prihvaćen eksperimetalni »model migrene«. U našem smo pokusu šarane tretirali s gliceril trinitratom intraperitonealno te smo odredili koncentraciju serumskih nitrita i nitrata, ispitali propusnost krvno-moždane barijere i analizirali histopatološke promjene u tkivu mozga. Koncentracija serumskih nitrita i nitrata imala je karakterističan bifazični obrazac s blagim inicijalnim i maksimalnim terminalnim povećanjem što sugerira GTN-induciranu endogenu NO sintezu. GTN-tretirane životinje su pokazale povećanu propusnost krvno-moždane barijere, što smo utvrdili na temelju istjecanja Evans blue boje u moždano tkivo. Histopatološkom analizom ustanovljene su promjene karakteristične za vazodilataciju i edem. Naše istraživanje snažno podupire važnu ulogu NO u patogenezi migrenskog napadaja, odnosno povećanje propusnosti krvno-moždane barijere u migrenskom napadaju. Ovo istraživanje također dokazuje da je ovaj mehanizam djelovanja konzerviran do nižih kralješnjaka i zbog toga ga možemo smatrati važnim.

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