Vasogenic brain edema induced by arachidonic acid: role of extracellular arachidonic acid in blood-brain barrier dysfunction.
The effects of free arachidonic acid on the capillary permeability of normal rat brains were studied by measuring the regional uptake of [14C]aminoisobutyric acid by a quantitative autoradiographic technique. Intracerebral infusion of sodium arachidonate increased capillary permeability in a dose-dependent manner up to a concentration of 2 mmol/L. A high dose of arachidonic acid (more than 5 mmol/L) produced marked tissue destruction around the injection site (needle track) and increased capillary permeability less than 2 mmol/L arachidonic acid did. A time-course study demonstrated that about 80% of the maximum increase in capillary permeability produced by arachidonic acid was observed within 2 hours after the infusion was initiated. In addition, capillary permeability gradually increased with time up to 24 hours, after which it declined to about half of the maximum increase 48 hours after infusion. These effects of arachidonic acid on capillary permeability were localized within about 1.6 mm around the injection site. Pretreatment with dexamethasone did not completely, but did significantly, inhibit the arachidonic acid-induced increase in capillary permeability. The inhibitory effect of dexamethasone was completely suppressed by the administration of actinomycin D, which inhibits de novo protein synthesis, 1 hour before the treatment with dexamethasone. These results suggest that arachidonic acid, which is released and accumulated in the extracellular space, increases the capillary permeability of the brain in at least two different ways. One is the direct action of the arachidonic acid itself, which can stimulate perturbation of the membrane of the capillary endothelial cells, thus promoting an increase in capillary permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohnishi
T
T
Department of Neurosurgery, Osaka University Medical School, Japan.
Posner
J B
JB
Shapiro
W R
WR
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000633:toxicity; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001929:Brain Edema / Q000139:chemically induced* / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D002421:Caudate Nucleus; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D007263:Infusions, Parenteral; D008297:Male; D011699:Putamen; D051381:Rats; D011919:Rats, Inbred Strains
D003609:Dactinomycin; D016718:Arachidonic Acid; D003907:Dexamethasone