Protective effect of a 21-aminosteroid on the blood-brain barrier following subarachnoid hemorrhage in rats.
The effects of subarachnoid injection of blood on blood-brain barrier permeability to albumin was assessed in a rat model. Subarachnoid injection of blood caused a significant sixfold increase in Evans blue extravasation, whereas sham operation or NaCl injection had no effect. In addition, subarachnoid injections of arachidonic acid or FeCl2 increased blood-brain barrier permeability to Evans blue 16- and 10-fold, respectively. The capillary permeability after subarachnoid injection of blood was normalized by pretreatment with a novel 21-aminosteroid, U-74006F, that has antioxidant and antilipolytic activity. Pretreatment with U-74006F also reduced the vascular leakage induced by subarachnoid injection of arachidonic acid or FeCl2 by 50% and 45%, respectively. We conclude that damage to membrane lipids by peroxidative and/or lipolytic processes is involved in the subarachnoid hemorrhage-induced blood-brain barrier opening and that U-74006F protects the blood-brain barrier against the effects of subarachnoid hemorrhage by preventing or limiting these pathologic membrane lipid changes.
Zuccarello
M
M
Veterans Administration Medical Center, Cincinnati, OH 45220.
Anderson
D K
DK
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology; D008297:Male; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000139:chemically induced / Q000503:physiopathology*
D001095:Arachidonic Acids; D005296:Ferrous Compounds; D011281:Pregnatrienes; D012709:Serum Albumin; D016718:Arachidonic Acid; D005070:Evans Blue; C029451:ferrous chloride; C053355:tirilazad