Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 39, Issue 1-3, Pages 8-14Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2009.10.002
Keywords
Ginkgolide B; Blood brain barrier; Middle cerebral artery occlusion; LC-MS/MS; Therapeutic time window
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The goal of this study was to estimate the blood brain barrier (BBB) permeability of Ginkgolide B in normal condition and models of ischemia both in vivo and in vitro. A sensitive LC-MS/MS analytical method was developed to determinate accurately the concentration of Ginkgolide B in cell, plasma and brain tissue. The injured rat brain microvessel endothelial cells (RBMECs) induced by Na2S2O4 served as a hypoxia/reoxygenation model in vitro. Intracellular concentration of Ginkgolide B increased in injured cells in a concentration-dependent manner. As a model of in vivo-ischemia/reperfusion, we performed middle cerebral artery occlusion (MCAC)in rats. Concentration of Ginkgolide B in the brain tissues showed higher in cerebral ischemia-reperfused animals than that in normal rats. To evaluate potential clinical effect of Ginkgolide B, we determined therapeutic time window in MCAO rats. Up to i.v. administration at 2 h after reperfusion of rats, Ginkgolide B Could decrease infarction volume and brain edema, exerting significant protective effect in cerebral ischemia injury. In conclusion, Ginkgolide B could pass through BBB, especially after ischemia-reperfusion injury of brain, and might be therapeutically effective for ischemia/reperfusion injury of human brain. (C) 2009 Elsevier B.V. All rights reserved.
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