Measurement of Solute Transport Across the Blood–Brain Barrier in the Perfused Guinea Pig Brain: Method and Application to N‐Methyl‐α‐Aminoisobutyric Acid
Measurement of Solute Transport Across the Blood–Brain Barrier in the Perfused Guinea Pig Brain: Method and Application to N‐Methyl‐α‐Aminoisobutyric Acid
复制标题
灌流豚鼠脑中溶质跨血脑屏障转运的测量：N-甲基-α-氨基异丁酸的方法和应用
DOI：
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发表时间：
1986
影响因子：
4.7
通讯作者：
D. Mitrović
中科院分区：
文献类型：
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作者：
B. Zlokovic;D. Begley;B. Djuričić;D. Mitrović
文摘：建立了一种活体豚鼠头部血管灌流技术，该技术适用于测量动脉流入受控条件下的血到脑转运。在灌流压在13到18kPa5到5.5kPa时，用[14C]丁醇测量的脑血流量，在同侧大脑皮质、海马体和尾壳核中约为1ml−1g−1；在小脑和脑桥白质中，它要小得多，需要更高的灌流压力才能在整个大脑中建立相等的血流量。灌流与非灌流10min后，同侧脑组织含水量、Na+/K+比值、三磷酸腺苷、能荷电位和乳酸含量无明显差异。灌流30min后，D-[~3H]甘露醇间隙未超过1%，表明屏障完整。在此期间，脑电、心电和呼吸波形保持正常。当[14C]N-甲基-α-氨基异丁酸(MeAIB)和D-[~3H]甘露醇一起灌流至30min时，可以测量顶叶皮质对这两种溶质的渐进性摄取，并根据多个时间摄取数据估计单向转移常数。MeAIB(0.75×10−3mlmin−1g−1)的KIN约为甘露醇的3倍。结论：该技术提供了一个稳定的、可控的同侧大脑半球微血管环境，适合于研究缓慢渗透的溶质进入大脑的传输。
Abstract: A technique for the vascular perfusion of the guinea pig head in vivo, suitable for measurements of blood‐to‐brain transport under controlled conditions of arterial inflow, has been developed. With a perfusion pressure ranging between 13 and 18 kPa and Pco2 in the arterial inflow of 5 and 5.5 kPa, cerebral blood flow, measured with [14C]butanol, was about 1 ml min−1 g−1 in the cerebral cortex, hippocampus, and caudate‐putamen of the ipsilateral hemisphere; in the cerebellum and pontine white matter it was considerably less, and much higher perfusion pressures were required to establish equal blood flow throughout the whole brain. Regional water content, Na+/K+ ratio, ATP, energy charge potential, and lactate content of the ipsilateral side of perfused and nonperfused brain were not significantly different after 10 min perfusion. The D‐[3H]mannitol space did not exceed 1% after 30 min of perfusion, indicating the integrity of the barrier. Over this period, EEG, ECG, and respiratory waveform remained normal. When [14C]N‐methyl‐α‐aminoisobutyric acid (MeAIB), and D‐[3H]mannitol were perfused together over periods extending to 30 min progressive uptakes of both solutes by the parietal cortex could be measured, and the unidirectional transfer constants estimated from multiple time‐uptake data. The Kin for MeAIB (0.75 × 10−3 ml min−1 g−1) was some three times that for mannitol. It is concluded that the technique provides a stable, well‐controlled environment in the cerebral microvasculature of the ipsilateral perfused brain hemisphere suitable for examining the transport of slowly penetrating solutes into the brain.