dl-3-n-butylphthalide attenuates reperfusion-induced blood-brain barrier damage after focal cerebral ischemia in rats.

Abstract

Aim: To study the protective effect of dl-3-n-butylphthalide (NBP) on blood-brain barrier (BBB) damage induced by reperfusion following focal cerebral ischemia.

Methods: Focal cerebral ischemia in rats was performed by inserting a nylon suture into intracranial segment of internal carotid artery to block the origin of middle cerebral artery and reperfusion by withdrawing the nylon suture. Permeability of BBB was determined by extravasation of the protein-bound Evans blue dye to cerebral cortex and further evaluated by immunohistochemical or electronmicroscopic method.

Results: Reperfusion for 3 h following focal cerebral ischemia for 3 h produced BBB damage which exhibited the increase in extravasation in cerebral cortex, elevation of the expression of immunoglobulin (IgG), and pore formation in endothelial cell membrane of capillary in cerebral cortex. NBP (5-20 mg.kg-1) decreased the extravasation in a dose-dependent manner. The expression of IgG in cerebral cortex was decreased and the ultrastructure damage of capillaries was alleviated after treatment with NBP. NBP 20 mg.kg-1 also alleviated brain edema caused by 3-h reperfusion following 3-h middle cerebral artery occlusion (MCAO).

Conclusion: NBP has protective effect on BBB damage induced by reperfusion after MCAO.