Contribution of dead-space microdomains to tortuosity of brain extracellular space
Contribution of dead-space microdomains to tortuosity of brain extracellular space
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DOI：
10.1016/j.neuint.2003.11.011
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发表时间：
2004-09-01
影响因子：
4.2
通讯作者：
Nicholson, C
中科院分区：
文献类型：
--
作者：
Hrabetov치, S;Nicholson, C
脑的细胞外空间（ECS）是细胞间通讯、营养和代谢物运输以及药物递送的主要通道。主要的传输机制是扩散，这是由两个结构参数，弯曲度和体积分数。弯曲度（λ）表示与无障碍介质相比由组织施加在扩散分子上的阻碍，而体积分数（α）是ECS占据的组织体积的比例。可以利用小ECS标记物的扩散来测量λ和α。在健康的脑组织中，α约为1.6，但在涉及细胞肿胀的病理中增加至1.9-2.0。以前，人们认为λ可以用扩散分子在细胞周围的环绕来解释。然而，凸单元组件的数值模型给出了λ的上限约为1.23。因此，额外的因素必须负责;在大脑中。原则上，两种机制可以解释测量值：更复杂的ECS几何形状或细胞外大分子基质。在这里，我们回顾了最近的工作，缺血组织凹的几何形态，死腔微区，作为一个主要的决定因素细胞外迂曲。基于扩散停留时间的λ理论模型支持这一假设，并预测，在缺血，死腔占据ECS体积分数的约60%，只留下约40%的连接良好的通道。进一步提出死腔存在于健康脑组织中，其中它们构成脑组织的约40%。ECS中死腔微区的存在意味着细胞外通道的微观异质性，对脑中的分子转运具有根本意义。(C)2003 Elsevier Ltd.保留所有权利。
The extracellular space (ECS) of the brain is a major channel for intercellular communication, nutrient and metabolite trafficking, and drug delivery. The dominant transport mechanism is diffusion, which is governed by two structural parameters, tortuosity and volume fraction. Tortuosity (lambda) represents the hindrance imposed on the diffusing molecules by the tissue in comparison with an obstacle-free medium, while volume fraction (alpha) is the proportion of tissue volume occupied by the ECS. Diffusion of small ECS markers can be exploited to measure lambda and alpha. In healthy brain tissue,; is about 1.6 but increases to 1.9-2.0 in pathologies that involve cellular swelling. Previously it was thought that lambda could be explained by the circumnavigation of diffusing molecules around cells. Numerical models of assemblies of convex cells, however, give an upper limit of about 1.23 for lambda. Therefore, additional factors must be responsible for; in brain. In principle, two mechanisms could account for the measured value: a more complex ECS geometry or an extracellular macromolecular matrix. Here we review recent work in ischemic tissue suggesting concave geometrical formations, dead-space microdomains, as a major determinant of extracellular tortuosity. A theoretical model of lambda based on diffusion dwell times supports this hypothesis and predicts that, in ischemia, dead spaces occupy approximate to60% of ECS volume fraction leaving only approximate to40% for well-connected channels. It is further proposed that dead spaces are present in healthy brain tissue where they constitute about 40% of a. The presence of dead-space microdomains in the ECS implies microscopic heterogeneity of extracellular channels with fundamental implications for molecular transport in brain. (C) 2003 Elsevier Ltd. All rights reserved.