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.
Lee
E-Jian
EJ
Neurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, Taiwan. ejian@mail.ncku.edu.tw
Chen
Hung-Yi
HY
Wu
Tian-Shung
TS
Chen
Tsung-Ying
TY
Ayoub
Issam A
IA
Maynard
Kenneth I
KI
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