Microdialysis as a method to study blood- brain barrier transport mechanisms
Microdialysis as a method to study blood- brain barrier transport mechanisms
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DOI：
10.1016/s1569-7339(06)16029-4
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
de Lange, Elizabeth C. M.
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文献类型：
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作者：
de Lange, Elizabeth C. M.
通常，血脑屏障（BBB）的运输仍被定性地认为是“有限的”或“容易的”。然而，对于给定的化合物，血脑屏障运输的速率和程度将是许多可能的被动和主动动态调节运输机制共同作用的最终结果。这意味着了解血脑屏障的运输机制和调控对于理解大脑稳态至关重要；一方面深入了解其干扰如何导致中枢神经系统疾病，另一方面最终能够预测中枢神经系统活性化合物的动力学和动力学之间的关系。在许多研究血脑屏障运输的体内技术中，体内微透析具有重要的独特特征，可以提供体内细胞外（EC）空间中游离浓度的数据。这一特性使得微透析作为研究血脑屏障转运动力学的一种技术特别有价值。在本章中，重点是使用脑内微透析技术来研究血脑屏障的运输和（在）脑内分布。总共使用了282个参考文献。在II中介绍了血脑屏障功能的决定因素，并介绍了影响血脑屏障功能的情况。然后，第三部分涉及研究血脑屏障转运的体内技术，包括微透析。随后，第四部分介绍了决定微透析结果有效性的关键方法学因素，利用微透析、脑组织和血浆/血液数据建立血脑屏障运输药代动力学模型的方法。然后，在V中，介绍了目前关于微透析血脑屏障转运研究的综述，其次是最近关于被动和主动血脑屏障转运机制的原始论文，以及其在许多疾病条件下的潜在变化。最后（VI），我们得出结论，将微透析与脑组织和血浆/血液数据结合使用，为在多种条件下表征许多物种血脑屏障运输机制提供了一种很好的方法。
Often, blood-brain barrier (BBB) transport is still considered qualitatively, in terms of "limited'' or "readily''. However, for a given compound, the rate and extent of BBB transport will be the net result of the contribution of many possible passive and active dynamically regulated transport mechanisms. This implies that knowledge of BBB transport mechanisms and regulation is critical for the understanding of brain homeostasis; on one hand to gain insights into how disturbances thereof may lead to CNS diseases, and on the other hand to ultimate being able to predict the relation between the kinetics and the dynamics of CNS active compounds. Among a number of in vivo techniques to study BBB transport, in vivo microdialysis has the important unique characteristic to provide data on free concentrations in the extracellular (EC) spaces in the body. This characteristic makes microdialysis especially valuable as a technique to study the kinetics of BBB membrane transport.In this chapter, the focus is on the use of intracerebral microdialysis technique to study BBB transport and (within) brain distribution. A total of 282 references are used. Following introduction, in II, the determinants in BBB functionality are presented with circumstances that affect BBB functionality. Then, part III deals with in vivo techniques to study BBB transport, including microdialysis. Subsequently part IV presents crucial methodological factors that determine the validity of microdialysis outcomes, approaches in pharmacokinetic modelling of BBB transport using microdialysis, brain tissue and plasma/blood data. Then, in V, the currently available reviews on BBB transport studies with microdialysis are presented, followed by the more recent original papers dealing with passive and active BBB transport mechanisms, as well as potential changes thereof in a number of disease conditions. Finally (VI), it is concluded that the use of microdialysis combined with brain tissue and plasma/blood data provides a good approach in characterising BBB transport mechanisms in many species, under a variety of conditions.