Acute administration of Ginkgo biloba extract (EGb 761) affords neuroprotection against permanent and transient focal cerebral ischemia in Sprague-Dawley rats.
We examined the neuroprotective action of a standardized extract of Ginkgo biloba leaves (EGb 761) in permanent and transient middle cerebral artery (MCA) occlusion models in Sprague-Dawley rats. Forty-four animals were given either EGb 761 (50-200 mg/kg) or vehicle intraperitoneally, 1 hr before permanent MCA occlusion, to evaluate the dose-response effects. An additional 58 animals received EGb 761 (200 mg/kg) or vehicle, 0.5- 4 hr after permanent MCA occlusion, for establishing the therapeutic window. Delayed treatment was also employed in 110 animals treated with either EGb 761 (100-200 mg/kg) or vehicle at 2-3 hr following transient focal cerebral ischemia induced by MCA occlusion for 2 hr. Neurobehavioral scores were determined 22-24 hr after permanent MCA occlusion and either 3 or 7 days after transient MCA occlusion, and brain infarction volumes were measured upon sacrifice. Local cortical blood flow (LCBF) was serially measured in a subset of animals receiving EGb 761 (100-200 mg/kg) or vehicle, 0.5 hr and 2 hr after permanent and transient MCA occlusion, respectively. Relative to vehicle-treated controls, rats pretreated with EGb761 (100 and 200 mg/kg) had significantly reduced infarct volumes, by 36% and 49%, respectively, and improved sensory behavior (P < 0.05). Delayed treatment with EGb 761 also significantly reduced brain infarction, by 20-29% and 31%, when given up to 2 and 3 hr following transient and permanent MCA occlusion, respectively, whereas improved neurobehavioral scores were noted up to 2 hr after the onset of MCA occlusion (P < 0.05). LCBF was significantly improved in the ipsilateral cortex following the EGb 761 treatment, whereas a higher dose showed a more sustained effect. In conclusion, EGb 761 protected against transient and permanent focal cerebral ischemia and was effective after a prolonged reperfusion period even when therapy is delayed up to 2 hr. This neuroprotection may be at least partially attributed to the beneficial effects of selectively improved LCBF in the area at risk of infarction.
Neurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, Taiwan. ejian@mail.ncku.edu.tw
E-Jian
EJ
Lee
Hung-Yi
HY
Chen
Tian-Shung
TS
Wu
Tsung-Ying
TY
Chen
Issam A
IA
Ayoub
Kenneth I
KI
Maynard
D000818:Animals; D001522:Behavior, Animal; D002560:Cerebrovascular Circulation / Q000187:drug effects; D020441:Ginkgo biloba; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss; D000096983:Ginkgo Extract
D018696:Neuroprotective Agents; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract