Efeitos do extrato de Ginkgo biloba, EGb 761, em ratos submetidos à isquemia cerebral : uma análise histológica e comportamental

• Ano de defesa: 2006
• Autor(a) principal: Paganelli, Ricardo Alexandre
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual de Maringá; Brasil; Programa de Pós-Graduação em Ciências Farmacêuticas; UEM; Maringá, PR; Departamento de Farmácia e Farmacologia
• Palavras-chave em Português: Isquemia cerebral; Efeito neuroprotetor; Ginkgo biloba (EGb 761); Labirinto Radial Aversivo; Brasil.; Rats; Cerebral ischemia; Tebonin®; EGb 761; Neuroprotection; Aversive radial maze; Brazil.; Ciências da Saúde; Farmácia
• Link de acesso: http://repositorio.uem.br:8080/jspui/handle/1/1930

The standardized extract of Ginkgo biloba L., EGb 761, has been used to treat several SNC related disorders, including those from hypoxic/ischemic nature. The antagonism of platelet activating factor (PAF) receptors and a reduction in PAF levels which increase during ischemia, as well as a potent antioxidative effect are belivied to contribute to the neuroprotective properties of EGb 761. Neuroprotection by EGb 761 has also been demonstrated in vivo animal models of cerebral ischemia. However, there is a paucity of studies aiming to investigate whether EGb 761 could facilitate behavioral recovery from ischemic brain damage. In both young and old, intact animals, EGb 761 has been shown to improve cognitive performance measured in different behavioral testing. Therefore, in the present study, we used the rat 4-vessel occlusion model (4-VO) to evaluate the effects of EGb 761 on ischemia-induced hippocampal damage and learning/memory impairments. This study was divided in two parts. Firstly, EGb 761 was delivered as the commercial product Tebonin® (EGb 761, oral solution, 40 mg/ml), in doses of 10, 40 or 100 mg/kg/day, p.o., for 14 days before ischemia. In other groups, Tebonin® was given at 40 or 100 mg/kg/day, for 14 days before plus 7 days after ischemia. The degree of hippocampal damage in the CA1 region was assessed 7 days after ischemia. Fifteen minutes 4-VO caused marked neurodegeneration (p <0.001, sham vs. ischemic). However, Tebonin® failed to provide CA1 neuroprotection, whatever the treatment used (p > 0.05, Tebonin vs. water). In the second part of this study, the originally manufactured, dry extract form of EGb 761 (50 or 150 mg/kg/day) was given orally, starting before ischemia and continuing for up 3 days after ischemia. Learning and memory performances were assessed in a non-food motivated, aversive radial maze task. The effects of EGb 761 on acquisition (learning) and retention (memory) performances, were investigated. In the acquisition experiment, rats were rendered ischemic, and 23 days later they were tested for acquisition performance (post-operative training). In the retention experiment, rats were trained for 10 days and then subjected to ischemia (pre-operative training); the retention of cognition 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. TGCI markedly disrupted both acquisition and retention performance (p < 0.001 - 0.05). EGb 761 (150 mg/kg) 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). 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, given as the dry extract, 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 failure of Tebonin® in protecting hippocampal cell from ischemia-induced neurodegeneration can not be explained from the present study, but we have hypothesized that one dose /day may not be sufficient to afford a sustained and adequate concentration of EGb 761 into the brain, at least in the rat.