Possible mechanism of vasogenic brain oedema induced by arachidonic acid.
Free arachidonic acid was infused into normal rat brains and the effect of arachidonic acid on capillary permeability was investigated by measuring the regional uptake of 14C-aminoisobutyric acid with a quantitative autoradiographic method. Arachidonic acid increased capillary permeability in a dose-dependent manner up to 2 mM. A high dose of arachidonic acid (greater than 5 mM) produced a profound tissue destruction around the needle track and less increased capillary permeability than 2 mM arachidonic acid. Time-course study disclosed that arachidonic acid markedly increased capillary permeability within 2 hours after infusion, and continued to increase with time to 24 hours. The effect of 48 hours infusion was about a half of that at 24 hours, indicating that the effect of arachidonic acid was partially reversible. Pretreatment with dexamethasone significantly inhibited the arachidonic acid-induced increase in capillary permeability and the administration of actinomycin D 1 hour before the pretreatment with dexamethasone suppressed the inhibitory effect of dexamethasone. These results suggest that arachidonic acid, which is deposited in the extracellular space, increases brain capillary permeability by two different ways. One is the direct detergent effect of arachidonic acid, and the other is the effect of arachidonic acid that is released from the membrane by the activation of phospholipase A2.
Ohnishi
T
T
Department of Neurosurgery, Osaka University Medical School, Japan.
Iwasaki
H
H
Hayakawa
T
T
Shapiro
W R
WR
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001345:Autoradiography / Q000379:methods; D001929:Brain Edema / Q000139:chemically induced* / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D003907:Dexamethasone