Blood brain barrier permeability and therapeutic time window of Ginkgolide B in ischemia-reperfusion injury.
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 Na(2)S(2)O(4) 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 (MCAO) 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 2h 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.
Fang
Weirong
W
Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
Deng
Yan
Y
Li
Yunman
Y
Shang
Erxin
E
Fang
Fang
F
Lv
Peng
P
Bai
Li
L
Qi
Yan
Y
Yan
Fang
F
Mao
Lishun
L
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004227:Dithionite; D042783:Endothelial Cells / Q000378:metabolism; D046934:Ginkgolides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D007783:Lactones / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D013997:Time Factors; D014018:Tissue Distribution
D046934:Ginkgolides; D007783:Lactones; D004227:Dithionite; C045856:ginkgolide B