High-dose methylprednisolone and 'ex vivo' release of eicosanoids after experimental subarachnoid haemorrhage.
In the present study we have investigated the effects of high-dose methylprednisolone (MP) treatment on the 'ex vivo' release of four major eicosanoids in an experimental model of subarachnoid haemorrhage (SAH) with the aim of verifying: (a) the efficacy in reducing arachidonic acid metabolism enhancement; (b) whether high-dose methylprednisolone is effective on both the cyclooxygenase and lipoxygenase pathways; and (c) discussing the possible role of high-dose MP treatment in brain protection after SAH. Levels of prostaglandin D2 and E2, prostacyclin and also leukotriene C4 were determined by the radioimmunoassay technique after 1 h incubation of cerebral cortex samples of rats which had been subjected to experimental SAH procedure (injection of 0.3 ml of autologous arterial blood). The release of prostaglandin D2 at 48 h after SAH is significantly higher when compared to that of sham-operated animals (P less than 0.01); prostaglandin E2 release is significantly enhanced at 6 h after the SAH procedure (P less than 0.01); release of the lipoxygenase metabolite is significantly enhanced at 1, 6 and 48 h after SAH induction; MP significantly decreases the release of all eicosanoids, and values in treated animals do not differ from those of sham-operated animals. The results of the present study suggest that the global inhibitory effect of high-dose MP treatment on the 'ex vivo' release of eicosanoids after experimental SAH could be considered to be one of the neurochemical correlates for the reduced incidence and severity of arterial inflammatory response, which results in chronic vasospasm and supports the clinical evidence of MP efficacy in preventing or reducing the incidence of arterial vasospasm after aneurysmal rupture.
Gaetani
P
P
Department of Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy.
Marzatico
F
F
Renault
B
B
Fulle
I
I
Lombardi
D
D
Ferlenga
P
P
Rodriguez y Baena
R
R
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002540:Cerebral Cortex / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013189:SRS-A / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000503:physiopathology
D015777:Eicosanoids; D013189:SRS-A; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D015230:Prostaglandin D2