Characterization of Seizure‐Induced Cysteinyl‐Leukotriene Formation in Brain Tissue of Convulsion‐Prone Gerbils

Abstract

Tonic-clonic seizures elicited in convulsion-prone gerbils resulted in a large increase in immunoreactive prostaglandin (PG) F2 alpha and in a smaller increase in immunoreactive leukotriene (LT) C4-like material in brain tissue. Brain tissue contents of both eicosanoids were found to reach a maximum at 6 min after the onset of seizures and were still elevated at 54 min after the beginning of convulsions. By reversed phase HPLC the immunoreactive LTC4-like material was identified as LTC4 and LTD4 at 6 min after the onset of convulsions, whereas at 54 min after the onset, transformation of LTD4 to LTE4 could be detected as well. In gerbils showing only weak seizure activity a small increase in PGF2 alpha but no increase in immunoreactive LTC4-like material could be detected at 6 min after the onset of convulsions. Pretreatment with indomethacin abolished the formation of PGF2 alpha but significantly enhanced the biosynthesis of immunoreactive LTC4-like material at 18 min after the beginning of seizures. The results demonstrate formation of cysteinyl-LT following tonic-clonic convulsions in spontaneously convulsing gerbils which could be enhanced by inhibition of the cyclooxygenase pathway of arachidonic acid metabolism. Since cysteinyl-LT have potent biological actions in various organs this finding warrants further investigations on the potential role of cysteinyl-LT in the CNS.

The influence of one hyperbaric oxygen-induced seizure on brain eicosanoid content

“…Eicosanoid brain levels in the HBO group were not higher than in the AC group, despite some reports of PG and LT elevation during seizures of various origins (Försterman et al, 1983;Simmet et al, 1988), or during free-radical generation (Dubois et al, 1987;Smith et aL, 1988).…”

“…One could object that sampling conditions may have modified the results: decapitation and immediate immersion in liquid nitrogen, though imperfect, is classical (Bazan, 1970;Försterman et aL, 1983;Lindgren et aL, 1984;Simmet et aL, 1988). If the brain remains in the head for 1 mm, there is little difference between microwave irradiation and decapitation in terms of levels of free fatty acid (Ceriedella et aL, 1975).…”

“…No previous data was available; moreover, since the hyperbaric environment prevented access to animals in real time, only stable eicosanoid metabolites could be used, in order to reflect global changes in metabolism; LTC4 was selected from among all leukotrienes because of its potential role in seizure (Simmet et al, 1988). Analyses were performed after the first seizure because only this seizure is HBO-specific; continuous exposition leads to status epilepticus and death, at which time the specificity of the initiating agent is lost among common and deep modifications in brain biochemistry, including prostanoids.…”

“…Electrically or chemically induced convulsions markedly increase free fatty acid content (Bazan, 1970;Siesjö et al, 1982) and subsequently PG content (Försterman et al, 1983) and LT (Simmet et al, 1988); this increase is not the only consequence of cerebral ischemia, a well-known stimulus of eicosanoid synthesis (FOrsterman et al, 1983), which may take place during some convulsions (SiesjO et a!., 1982). Ionizing radiations damage tissues and increase PG content (Dubois et a!., 1987); normobaric hyperoxia also damages tissues, but PG content varies with the considered tissue: it may decrease in vascular endothelium (an important target for both ionizing radiation and hyperoxia [Setty et a!., 1984]) or increase in lung bronchoalveolar lavage fluid (PG and LT content, Smith et a!., 1988).…”

Differential expression of arachidonate 5-lipoxygenase transcripts in human brain tumors: evidence for the expression of a multitranscript family.

“…This is supported by the findings that immunoreactive leukotriene C4 is present in the nerve endings in the median eminence and in cell bodies in the preoptic area (9). Although indirect evidence for leukotriene production in neuronal tissue was obtained in experimental animals (9,10) and humans (11), no direct determination of the 5-LO gene product has yet been performed for the human or experimental animal brain. Therefore, one of the purposes of the present study was to measure the abundance of the 5-LO transcript in bovine and human brain.…”