Cerebral ischemia-reperfusion (I/R)

Cerebral ischemia-reperfusion (I/R) injury usually contributes to mortality anddisability after ischemic stroke. Ginkgolides injection (GIn), a standard preparationcomposed of ginkgo diterpene lactones extract, is clinically used for neuroprotectivetreatment on reconvalescents of cerebral infarction. However, the understanding about itstherapeutic mechanism is still lacking. In this study, a gas chromatography-massspectrometry (GC-MS) based metabolomic approach coupled with multivariate dataanalysis (MVDA) was applied to explore the neuroprotective effects of GIn in a rodentmodel of focal ischemic stroke induced by transient middle cerebral artery occlusion(tMCAO). Metabolomic profiling revealed a series of metabolic perturbations thatunderlie the cerebral I/R pathological events. GIn can reverse the I/R induced brainmetabolic deviations by modulating multiple metabolic pathways, such as glycolysis,Krebs cycle, pentose phosphate pathway (PPP), γ-aminobutyrate (GABA) shunt and lipidmetabolism. Moreover, the main bioactive components of GIn were distributed to braintissue much more easily in tMCAO rats than in normal rats after an intravenousadministration, suggesting that the increased cerebral exposure to ginkgolides in I/Rpathological condition potentially facilitated the neuroprotective effects of GIn by directlytargeting at brain. The present study provided valuable information for our understandingabout metabolic changes of cerebral I/R injury and clinical application of GIn.