title: Sustained neuroprotection and facilitation of behavioral recovery by the Ginkgo biloba extract, EGb 761, after transient forebrain ischemia in rats.
abstract: The effects of the Ginkgo biloba extract, EGb 761, on ischemia-induced learning/memory impairments and hippocampal damage were evaluated in a non-food motivated, aversive radial maze task (AvRM). Rats were subjected to 15 min transient, global cerebral ischemia (TGCI). In the first experiment, rats were rendered ischemic, and 23 days later were tested for acquisition performance (post-operative training). In a second experiment, rats were trained for 10 days and then subjected to ischemia (pre-operative training); the retention of cognition performance was assessed on days 31, 35 and 39 after ischemia. Acquisition and retention performances were expressed by (a) latency to find a goal box, (b) number of reference memory errors, and (c) number of working memory errors. EGb 761 (50 or 150 mg/kg) was given orally, starting before ischemia and continuing for up to 3 days after ischemia. TGCI markedly disrupted both acquisition and retention performance (p < 0.001-0.05). EGb 761 (150 mg/kg) completely reversed acquisition impairment as measured by the parameters 'latency' and 'number of reference errors' when performance was examined across sessions (p < 0.01-0.05). The total number of reference errors was also completely abolished by EGb 761 (150 mg/kg). However, EGb 761 did not statistically reduce the effects of TGCI on the parameter 'working memory errors' (across session and total). At 50 mg/kg, EGb 761 did not affect ischemia-induced acquisition impairment at all. The retention deficit caused by ischemia was not statistically reduced by EGb 761 (150 mg/kg), whatever examined across session or as total. EGb 761 reduced the extent of hippocampal CA1 cell loss (p < 0.01-0.001), an effect sustained at least up to 40 days after ischemia. These findings show that EGb 761 is effective in reducing, at least partially, both the cognitive impairments and hippocampal damage after TGCI in rats, and suggest that its effect on behavioral recovery may be dissociated from the neuroprotective effect on the hippocampus. The present results also validate the AvRM as an alternative, reliable behavioral test to assess the effects of drugs on behavioral recovery after ischemic brain damage.
authors.affiliation: Department of Pharmacy and Pharmacology, Health Science Center, Pharmaceutical Sciences Post-Graduation Program, State University of Maringá, Av. Colombo 5790, CEP 87020-900 Maringá, Paraná, Brazil.
authors.forename: Ricardo Alexandre
authors.initials: RA
authors.lastname: Paganelli
authors.forename: Arcelio
authors.initials: A
authors.lastname: Benetoli
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020441:Ginkgo biloba; D006624:Hippocampus / Q000166:cytology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010936:Plant Extracts / Q000627:therapeutic use*; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects*; D000096983:Ginkgo Extract
chemical_list: D018696:Neuroprotective Agents; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract