Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center,Amarillo, Texas, USA.
J Pharm Pharm Sci. 2012;15(1):94-102. doi: 10.18433/j3ps37.
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.
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.
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.
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.
银杏叶提取物 EGb761 在各种实验模型中显示出抗水肿和抗缺血作用。在本研究中，我们通过微透析监测脑代谢来证明 EGb761 在实验性中风中的神经保护作用。
我们使用体外脑片氧葡萄糖剥夺和体内大脑中动脉闭塞 (MCAO) 来诱导小鼠脑缺血。我们使用微透析在小鼠纹状体监测细胞外葡萄糖和谷氨酸浓度。
在体外，EGb761 可将海马切片中缺血诱导的细胞肿胀减少 60%。在体内，EGb761（300mg/kg）给药可将 MCAO 后细胞变性和水肿形成减少 35-50%。MCAO 后，纹状体葡萄糖水平降至对照组的 25%，EGb761 对其无明显影响。相比之下，纹状体谷氨酸水平在 MCAO 后增加了 15 倍；用 EGb761 预处理后，谷氨酸水平仅增加了 4-5 倍。
我们表明，在缺血条件下，EGb761 的预处理可强烈减少细胞水肿形成和神经退行性变。作用机制似乎与减少兴奋性毒性有关，因为缺血诱导的谷氨酸释放被强烈抑制。银杏叶提取物如 EGb761 可能对预防易中风患者的缺血性损伤具有重要意义。
