Cerebral ischemia-reperfusion (I/R)

Cerebral ischemia-reperfusion (I/R) injury usually contributes to mortality and disability after ischemic stroke.Ginkgolides injection (GIn), a standard preparation composed of ginkgo diterpene lactones extract, is clinically used forneuroprotective treatment on reconvalescents of cerebral infarction. However, the understanding about its therapeuticmechanism is still lacking. In this study, a gas chromatography-mass spectrometry (GC-MS) based metabolomicapproach coupled with multivariate data analysis (MVDA) was applied to explore the neuroprotective effects of GIn in arodent model of focal ischemic stroke induced by transient middle cerebral artery occlusion (tMCAO). Metabolomicprofiling revealed a series of metabolic perturbations that underlie the cerebral I/R pathological events. GIn canreverse the I/R induced brain metabolic deviations by modulating multiple metabolic pathways, such as glycolysis,Krebs cycle, pentose phosphate pathway (PPP), g-aminobutyrate (GABA) shunt and lipid metabolism. Moreover, themain bioactive components of GIn were distributed to brain tissue much more easily in tMCAO rats than in normal ratsafter an intravenous administration, suggesting that the increased cerebral exposure to ginkgolides in I/R pathologicalcondition potentially facilitated the neuroprotective effects of GIn by directly targeting at brain. The present studyprovided valuable information for our understanding about metabolic changes of cerebral I/R injury and clinicalapplication of GIn.