Neuroprotective effects of bilobalide are accompanied by a reduction of ischemia-induced glutamate release in vivo.
Neuroprotective effects of bilobalide are accompanied by a reduction of ischemia-induced glutamate release in vivo.
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DOI：
10.1016/j.brainres.2011.10.005
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发表时间：
2011-11-24
期刊：
影响因子：
2.9
通讯作者：
Klein J
中科院分区：
文献类型：
--
作者：
Lang D;Kiewert C;Mdzinarishvili A;Schwarzkopf TM;Sumbria R;Hartmann J;Klein J
银杏内酯是银杏提取物的一种特殊成分，其神经保护特性在中风小鼠模型中进行了测试。大脑中动脉闭塞（MCAO）24小时后，在MCAO前1小时给予10 mg/kg白果内酯，可使核心区域（纹状体）的梗死面积减少40-50%。在较低剂量或在卒中诱导后1小时给予药物时也观察到神经保护作用。小鼠的感觉运动功能，白果内酯改善，如所示的角落和烟囱测试。当脑代谢原位监测微透析，MCAO引起细胞外葡萄糖在纹状体的迅速消失，再灌注后恢复到基线水平。细胞外谷氨酸水平在纹状体组织中增加了十倍以上，在海马组织（半影区）中增加了四到五倍。白果内酯不影响葡萄糖水平，但强烈衰减谷氨酸释放的核心和半影区。通过微透析探针局部给药时，白果内酯同样具有活性，并且在体外脑切片中也减少了缺血诱导的谷氨酸释放。我们得出结论，白果内酯是一种强大的神经保护剂，在体内剂量，可用于治疗人类。作用机制显然涉及减少谷氨酸释放，从而减少兴奋性毒性。
Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 hours of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40-50% when given at 10 mg/kg one hour prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the striatum which returned to baseline levels after reperfusion. Extracellular levels of glutamate were increased by more than ten-fold in striatal tissue, and by four- to fivefold in hippocampal tissue (penumbra). Bilobalide did not affect glucose levels but strongly attenuated glutamate release in both core and penumbra regions. Bilobalide was equally active when given locally via the microdialysis probe and also reduced ischemia-induced glutamate release in vitro in brain slices. We conclude that bilobalide is a strong neuroprotectant in vivo at doses that can be used therapeutically in humans. The mechanism of action evidently involves reduction of glutamate release, thereby reducing excitotoxicity.
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影响因子：
8.3
作者：
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影响因子：
3.3
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影响因子：
2.9
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影响因子：
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