Role of brain tissue leukotriene in brain oedema following cerebral ischaemia: effect of a 5-lipoxygenase inhibitor, AA-861.
It has been postulated that lipoxygenase metabolites of arachidonic acid play a role in the pathogenesis of cerebral ischaemia. Severe forebrain ischaemia in rats was induced by four-vessel occlusion with mild hypotension. After 30 min of ischaemia, circulation was restored by removing the arterial clamps and increasing blood pressure to preischaemic levels. During 30 min of cerebral ischaemia, free arachidonic acid increased by approximately 8.5 times compared with the preischaemic level. This accumulation was reversed within 60 min of reperfusion. The concentration of leukotriene C4 in brain tissue increased significantly during reperfusion: treatment with a 5-lipoxygenase inhibitor, AA-861, decreased the increase of brain water content associated with reperfusion. This study demonstrated that the increased arachidonic acid resulting from cerebral ischaemia in rats is metabolized to leukotrienes via the lipoxygenase pathway once circulation is restored, and these leukotrienes may play some role in the development of postischaemic cerebral oedema.
Mabe
H
H
Department of Neurosurgery, Nagoya City University Medical School, Japan.
Nagai
H
H
Suzuka
T
T
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D016227:Benzoquinones / Q000494:pharmacology*; D001834:Body Water / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D001929:Brain Edema / Q000209:etiology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications*; D001933:Brain Stem / Q000098:blood supply; D002531:Cerebellum / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000502:physiology; D004569:Electroencephalography; D005070:Evans Blue; D015289:Leukotrienes / Q000502:physiology*; D016859:Lipoxygenase Inhibitors; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D016227:Benzoquinones; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D005070:Evans Blue; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone