linoleic-acid and Seizures

Linoleic and alpha-linolenic polyunsaturated fatty acids, derived from plant oils, have been reported to reduce neuronal excitability ex vivo and in cell culture. The evidence derived from animal seizure models, however, has been contradictory. The goal of the present study was to assess the dose-dependent anticonvulsant effects of a fatty acid mixture containing linoleic and alpha-linolenic acids in a 4 to 1 ratio (the "SR-3" compound).. The maximal pentylenetetrazol seizure model and Long-Evans hooded rats were used.. Daily intraperitoneal injection of SR-3 for 21 consecutive days raised omega-3 polyunsaturated fatty acid (n-3 PUFA) composition in the unesterified fatty acid fraction of brain lipids (p < 0.05), and increased latency to seizure onset when administered at 200 mg/kg (p < 0.05), but not at 40 mg/kg (p > 0.05). There were no significant effects of SR-3 on seizure occurrence or on seizure severity (p > 0.05). A toxic effect of the SR-3 compound on peristalsis was observed at a dose of 400 mg/kg and above.. Linoleic and alpha-linolenic polyunsaturated fatty acids in a 4 to 1 ratio raises n-3 PUFA composition of unesterified fatty acids in the brain and increases resistance to pentylenetetrazol-induced seizures.

Topics: alpha-Linolenic Acid; Animals; Anticonvulsants; Brain; Convulsants; Dose-Response Relationship, Drug; Linoleic Acid; Pentylenetetrazole; Rats; Seizures

Recent studies have shown that long-chain polyunsaturated fatty acids can prevent cardiac arrhythmias, attributed to the reduction in excitability of cardiomyocytes, owing mainly to a shift in hyperpolarizing direction of the inactivation curves of both Na+ and Ca2+ currents and to a slowed recovery from inactivation. Qualitatively similar effects of polyunsaturated fatty acids on inactivation parameters have been observed in freshly isolated hippocampal neurons. Since the same effects are presumed to underlie the action of some established anticonvulsant drugs, polyunsaturated fatty acids might have an anticonvulsant action as well. We have investigated this for eicosapentaenoic acid, docosahexaenoic acid, linoleic acid and oleic acid, employing cortical stimulation in rats, a seizure model allowing the determination of the full anticonvulsant effect-time profile in freely moving, individual animals. I.v. infusion of 40 micromol of eicosapentaenoic acid or docosahexaenoic acid over a period of 30 min, modestly increased the threshold for localized seizure activity after 6 h by 73 +/- 13 microA (mean +/- S.E.M.; n = 7) and 77 +/- 17 microA (n = 7), respectively, and the threshold for generalized seizure activity by 125 +/- 20 and 130 +/- 19 microA, respectively (P < 0.001). The thresholds remained elevated for 6 h after infusion, but returned to baseline the next day. Free plasma concentrations in rats treated with eicosapentaenoic acid or docosahexaenoic acid, averaged 5.7 +/- 1.6 microM (n = 4) for eicosapentaenoic acid and 12.9 +/- 1.8 microM (n = 5) for docosahexaenoic acid at the end of infusion, but declined to undetectable levels within 3 h. Linoleic acid and oleic acid were less effective. Possible mechanisms for the modest anticonvulsant effect but of long duration with the polyunsaturated fatty acids are discussed.

Topics: Animals; Disease Models, Animal; Docosahexaenoic Acids; Electric Stimulation; Fatty Acids, Unsaturated; Linoleic Acid; Male; Oleic Acid; Outcome Assessment, Health Care; Rats; Rats, Wistar; Seizures; Valproic Acid