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丙二醇对血脑屏障通透性影响的定量评估。

Quantitative evaluation of the effect of propylene glycol on BBB permeability.

作者信息

Sood Rohit, Taheri Saeid, Estrada Eduardo Y, Rosenberg Gary A

机构信息

Department of Neurology, University of New Mexico, Albuquerque, New Mexico, USA.

出版信息

J Magn Reson Imaging. 2007 Jan;25(1):39-47. doi: 10.1002/jmri.20802.

DOI:10.1002/jmri.20802
PMID:17173307
Abstract

PURPOSE

To establish the blood-brain barrier (BBB) blocking property of propylene glycol (PG) using the (14)C sucrose technique, quantitatively evaluate the effect of PG on BBB permeability using an MRI technique based on graphical analysis, and demonstrate the sensitivity of MRI for testing newer investigational drugs.

MATERIALS AND METHODS

Brain uptake of sucrose was measured in treated (PG+) and untreated (PG-) rats using a (14)C sucrose technique in rat brains (N = 10) that had undergone two hours of middle cerebral artery occlusion (MCAO) and three hours of reperfusion. Another group of PG+ and PG- rats (N = 8) underwent MRI. T2-weighted (T2W) and diffusion-weighted (DW) images were acquired on a 4.7T MR system. A rapid T1 mapping protocol was implemented to acquire a baseline data set followed by postinjection data sets at regular intervals. The data were postprocessed pixelwise to generate permeability coefficient color maps.

RESULTS

A significant (P < 0.05) reduction in (14)C sucrose space was observed on the ischemic side of PG+ rats only. Permeability coefficient estimates obtained by MRI from the ipsilateral hemisphere in PG+ rats were significantly lower than those in PG- rats (P < 0.05). There was no significant change on the contralateral side in PG+ rats. The results show that PG protects the BBB in ischemic stroke, and MRI measurements are sufficiently sensitive to noninvasively detect small drug effects.

CONCLUSION

MRI is useful for evaluating the BBB blocking effect of PG in an ischemic stroke model of rat brain. The results from the MR experiment agree well with findings from the (14)C sucrose technique.

摘要

目的

使用¹⁴C蔗糖技术确定丙二醇(PG)的血脑屏障(BBB)阻断特性,基于图形分析的MRI技术定量评估PG对BBB通透性的影响,并证明MRI对测试新型研究药物的敏感性。

材料与方法

在经历了两小时大脑中动脉闭塞(MCAO)和三小时再灌注的大鼠脑(N = 10)中,使用¹⁴C蔗糖技术测量处理组(PG+)和未处理组(PG-)大鼠脑内蔗糖的摄取情况。另一组PG+和PG-大鼠(N = 8)接受MRI检查。在4.7T MR系统上采集T2加权(T2W)和扩散加权(DW)图像。实施快速T1映射协议以获取基线数据集,随后定期采集注射后数据集。对数据进行逐像素后处理以生成通透性系数彩色图。

结果

仅在PG+大鼠的缺血侧观察到¹⁴C蔗糖空间显著(P < 0.05)减少。通过MRI获得的PG+大鼠同侧半球的通透性系数估计值显著低于PG-大鼠(P < 0.05)。PG+大鼠的对侧没有显著变化。结果表明,PG在缺血性卒中中保护血脑屏障,并且MRI测量足够灵敏,能够无创检测小的药物效应。

结论

MRI可用于评估PG在大鼠脑缺血性卒中模型中的血脑屏障阻断作用。MR实验结果与¹⁴C蔗糖技术的结果非常吻合。

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