Brain Permeability of Bilobalide as Probed by Microdialysis Before and After Middle Cerebral Artery Occlusion in Mice
Brain Permeability of Bilobalide as Probed by Microdialysis Before and After Middle Cerebral Artery Occlusion in Mice
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DOI：
10.18433/j31c7q
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发表时间：
2010-01-01
影响因子：
2.7
通讯作者：
Klein, Jochen
中科院分区：
文献类型：
--
作者：
Lang, Dorothee;Ude, Christian;Klein, Jochen
目的。 Bilobalide 是银杏叶的活性成分，对脑缺血小鼠具有神经保护作用。在本研究中，我们研究了 (i) 健康小鼠和 (ii) 中风前后小鼠的白果内酯脑通透性。方法。我们使用体内微透析和 LC-MS 来估计白果内酯的细胞外水平。通过腹腔注射给予 10 mg/kg 白果内酯。对照小鼠注射，大脑中动脉闭塞（MCAO）前后 60 分钟。结果。注射后 10 分钟，脑纹状体微透析液中已可检测到白果内酯。 p。 40 分钟后达到最高水平（19 ng/mL，相当于 0.92 muM）。血浆白果内酯的最大水平为 5.9 μM。在缺血性损伤后，该药物可以以与对照小鼠相似的效率进行透析，表明从缺血性大脑中缓慢消除。当 MCAO 后给予药物时，大脑中的可用性较低，但可测量，约为 100%。控制值的 10%。结论。我们的数据表明，白果内酯很容易穿过血脑屏障并达到大脑中的细胞外浓度，从而可以与神经递质受体等目标分子有效相互作用。在缺血前给药时，药物在缺血组织中的利用率很高，但在 MCAO 后则严重受限。
Purpose. Bilobalide is an active constituent of Ginkgo biloba and has shown neuroprotective effects in mice with cerebral ischemia. In the present study, we investigated brain permeability of bilobalide (i) in healthy mice and (ii) in mice before or after stroke. Methods. We have used in vivo microdialysis and LC-MS to estimate extracellular levels of bilobalide. 10 mg/kg of bilobalide was given by i.p. injection to control mice, and 60 minutes before and after middle cerebral artery occlusion (MCAO). Results. Bilobalide was already detectable in brain striatal microdialysates 10 min after i. p. administration and reached maximum levels (19 ng/mL, corresponding to 0.92 mu M) after 40 min. Maximum plasma bilobalide levels were 5.9 mu M. After an ischemic insult, the drug could be dialysed with similar efficiency as in control mice indicating slow elimination from the ischemic brain. When the drug was given after MCAO, availability in the brain was low, but measurable, at approx. 10% of control values. Conclusions. Our data demonstrate that bilobalide easily crosses the blood brain barrier and reaches extracellular concentrations in the brain that allow efficient interaction with target molecules such as neurotransmitter receptors. Availability of the drug in ischemic tissue is high when given before ischemia, but severely limited after MCAO.