BLOOD-BRAIN-BARRIER TRANSPORT OF BUTANOL AND WATER RELATIVE TO N-ISOPROPYL-PARA-IODOAMPHETAMINE AS THE INTERNAL REFERENCE
BLOOD-BRAIN-BARRIER TRANSPORT OF BUTANOL AND WATER RELATIVE TO N-ISOPROPYL-PARA-IODOAMPHETAMINE AS THE INTERNAL REFERENCE
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DOI：
10.1038/jcbfm.1985.35
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发表时间：
1985-01-01
影响因子：
6.3
通讯作者：
FIERER, G
中科院分区：
文献类型：
--
作者：
PARDRIDGE, WM;FIERER, G
[14C]丁醇和[3H]水的BBB[血脑屏障]转运通过颈动脉注射技术在清醒和氯胺酮或戊巴比妥麻醉的大鼠中进行研究，使用N-异丙基-对[125I]碘苯丙胺([125I]IMP)作为内参和流体微球。 3种同位素（3H、125I、14C）在液体闪烁光谱仪中同时计数。在清醒的大鼠中，IMP 基本上被大脑完全隔离至少 1 分钟，在麻醉的动物中则被大脑完全隔离 2 分钟。大鼠前脑提取的丁醇不受流量限制，但范围在 77.+- 之间。 1 和 87 .+-。 3 个条件为 1%。前脑对丁醇的不完全提取是由于某些区域（额叶皮层、丘）丁醇清除的扩散限制，但在其他区域（尾状核、海马、嗅球）则不然。大鼠前脑中丁醇和水的渗透性-表面积乘积/脑血流量比保持相对恒定，为1.7±。 0.2 和 1.0.+-。尽管与戊巴比妥麻醉的大鼠相比，清醒状态下的脑血流量增加了 2 倍，但分别为 0.1。流量与丁醇或水提取之间不存在反比关系，这与毛细血管募集是麻醉中脑血流量变化的主要机制一致。丁醇的 BBB 转运在某些区域受到扩散限制，但在其他区域则不受限制，因此在使用该化合物作为脑血流标记物之前，需要对 BBB 对丁醇的渗透性进行仔细的区域分析。
The BBB [blood brain barrier] transport of both [14C]butanol and [3H]water was studied using the carotid injection technique in conscious and ketamine or pentobarbital anesthetized rats employing N-isopropyl-p-[125I]iodoamphetamine ([125I]IMP) as the internal reference and as a fluid microsphere. The 3 isotopes (3H, 125I, 14C) were counted simultaneously in a liquid scintillation spectrometer. IMP was essentially completely sequestered by the brain for at least 1 min in conscious rats and for 2 min in anesthetized animals. Butanol extraction by rat forebrain was not flow limited but ranges between 77 .+-. 1 and 87 .+-. 1% for the 3 conditions. The incomplete extracton of butanol by the forebrain was due to diffusion restriction of butanol clearance in some regions (frontal cortex, colliculi) but not in others (caudate, hippocampus, olfactory bulb). The permeability-surface area product/cerebral blood flow ratio of butanol and water in rat forebrain remains relatively constant, 1.7 .+-. 0.2 and 1.0 .+-. 0.1,respectively, despite a 2-fold increase in cerebral blood flow in conscious relative to pentobarbital-anesthetized rats. The absence of an inverse relationship between flow and butanol or water extraction was consistent with capillary recruitment being the principal mechanism underlying changes in cerebral blood flow in anesthesia. The diffusion restriction of BBB transport of butanol in some regions, but not in others, necessitates a careful regional analysis of BBB permeability to butanol prior to usage of this compound as a cerebral blood flow markers.