Protective effect of a 21-aminosteroid on the blood-brain barrier following subarachnoid hemorrhage in rats.

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Abstract
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.