title: Ginkgo extract EGb761 confers neuroprotection by reduction of glutamate release in ischemic brain.
abstract: OBJECTIVE
  Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis.
  
  
  METHODS
  We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate.
  
  
  RESULTS
  In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema formation after MCAO by 35-50%. Immediately following MCAO, striatal glucose levels dropped to 25% of controls, and this reduction was not significantly affected by EGb761. Striatal glutamate levels, in contrast, increased 15-fold after MCAO; after pretreatment with EGb761, glutamate levels only increased by 4-5fold.
  
  
  CONCLUSIONS
  We show that pretreatment with EGb761 strongly reduces cellular edema formation and neurodegeneration under conditions of ischemia. The mechanism of action seems to be related to a reduction of excitotoxicity, because ischemia-induced release of glutamate was strongly suppressed. Ginkgo extracts such as EGb761 may be valuable to prevent ischemia-induced damage in stroke-prone patients.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center,Amarillo, Texas, USA. klein@em.uni-frankfurt.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Mdzinarishvili
authors.forename: Rachita
authors.initials: R
authors.lastname: Sumbria
authors.forename: Dorothee
authors.initials: D
authors.lastname: Lang
authors.forename: Jochen
authors.initials: J
authors.lastname: Klein
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D020441:Ginkgo biloba; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000187:drug effects* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D017551:Microdialysis; D018696:Neuroprotective Agents / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D000096983:Ginkgo Extract
chemical_list: D005947:Glucose; D018698:Glutamic Acid; D018696:Neuroprotective Agents; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract