Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis

We investigated the influence of recurrent epileptic seizures on the arachidonic acid (AA) cascade in platelets and brain microvessels, using [¹⁴C]AA as a tracer substrate and chromatographic determination. The recurrent epileptic seizures of male Wistar rats were induced every second day with 3-aminopyridine (3-AP, 25 mg/kg ip) for two weeks. In the chronic 3-AP model, the earlier epileptic insults resulted in a decreased incidence of limbic seizures and higher survival rate at later administration of 3-AP. After 3-AP treatment, the formation of lipoxygenase products was unchanged, but the total amount of cyclooxygenase (COX) metabolites was decreased both in platelets and brain microvessels. The reduction in COX-mediated eicosanoid synthesis after recurrent seizures was due to the decreased synthesis of vasodilator and vasoconstrictor COX metabolites. In platelets, the 3-AP-treatment reduced the synthesis of vasodilator prostacyclin (PGI₂), prostaglandin E₂ (PGE₂) and 12-L-hydroxy-5,8, 10-heptadecatrienoic acid (12-HHT), while the synthesis of prostaglandin D₂ (PGD₂) remained unchanged. In isolated brain capillaries, the PGD₂, PGE₂ and 12-HHT synthesis was decreased after recurrent seizures. As for the vasoconstrictor COX metabolites, both platelets and brain microvessels synthesized significantly lesser amount of prostaglandin F_2α (PGF_2α) and thromboxarie A₂ (TxA₂) upon 3-AP administration. Our results indicate that platelets and isolated brain capillaries synthesize significantly lesser amount of COX metabolites after chronic 3-AP treatment. The decreased conversion of AA into different COX products may play a role in the neuroprotective/preconditional adaptation of the brain against subsequent seizures.