Diffusion in brain extracellular space.
Diffusion in brain extracellular space.
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DOI：
10.1152/physrev.00027.2007
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发表时间：
2008-10
影响因子：
33.6
通讯作者：
Nicholson C
中科院分区：
文献类型：
--
作者：
Syková E;Nicholson C
脑细胞外间隙（ECS）中的扩散受体积分数和迂曲度的约束，并且修正的扩散方程代表了许多分子在脑中的运输行为。与方程的偏差揭示了通过细胞摄取、结合或其他机制穿过血脑屏障的分子损失。早期的扩散测量使用放射性标记的蔗糖和其他示踪剂。目前，实时离子电渗（RTI）方法用于小离子和集成光学成像（IOI）方法用于荧光大分子，包括葡聚糖或蛋白质。ECS的理论模型和模拟已经探索了ECS的几何形状的影响，死腔微区的影响，细胞外基质和大分子与ECS通道的相互作用。在正常脑组织中使用阳离子四甲基铵（TMA）的RTI方法的广泛实验研究表明，ECS的体积分数通常约为20%，弯曲度约为1.6（即TMA的自由扩散系数降低了2.6），尽管存在区域变化。这些参数在发育和老化过程中发生变化。扩散特性已在几种干预措施中表征，包括脑刺激、渗透压挑战和细胞外基质成分敲除。在局部缺血、阿尔茨海默病和帕金森病模型以及人类神经胶质瘤中也进行了测量。总之，这些研究提高了我们的概念ECS的结构和胶质细胞和细胞外基质在调节ECS微环境的作用。ECS的扩散特性的知识是有价值的背景下，从了解突触外体积传输的发展范式药物输送到大脑。
Diffusion in the extracellular space (ECS) of the brain is constrained by the volume fraction and the tortuosity and a modified diffusion equation represents the transport behavior of many molecules in the brain. Deviations from the equation reveal loss of molecules across the blood-brain barrier, through cellular uptake, binding or other mechanisms. Early diffusion measurements used radiolabeled sucrose and other tracers. Presently, the real-time iontophoresis (RTI) method is employed for small ions and the integrative optical imaging (IOI) method for fluorescent macromolecules, including dextrans or proteins. Theoretical models and simulations of the ECS have explored the influence of ECS geometry, effects of dead-space microdomains, extracellular matrix and interaction of macromolecules with ECS channels. Extensive experimental studies with the RTI method employing the cation tetramethylammonium (TMA) in normal brain tissue show that the volume fraction of the ECS typically is about 20% and the tortuosity about 1.6 (i.e. free diffusion coefficient of TMA is reduced by 2.6), although there are regional variations. These parameters change during development and aging. Diffusion properties have been characterized in several interventions, including brain stimulation, osmotic challenge and knockout of extracellular matrix components. Measurements have also been made during ischemia, in models of Alzheimer's and Parkinson's diseases and in human gliomas. Overall, these studies improve our conception of ECS structure and the roles of glia and extracellular matrix in modulating the ECS microenvironment. Knowledge of ECS diffusion properties are valuable in contexts ranging from understanding extrasynaptic volume transmission to the development of paradigms for drug delivery to the brain.
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DOI：
10.1006/meth.1999.0771
发表时间：
1999-06-01
期刊：
METHODS-A COMPANION TO METHODS IN ENZYMOLOGY
影响因子：
--
作者：
Andrew, RD;Jarvis, CR;Obeidat, AS
通讯作者：
Obeidat, AS
影响因子：
4.8
作者：
Aitken, PG;Fayuk, D;Turner, DA
通讯作者：
Turner, DA
DOI：
10.1016/0160-5402(89)90012-0
发表时间：
1989-11-01
期刊：
JOURNAL OF PHARMACOLOGICAL METHODS
影响因子：
--
作者：
AMBERG, G;LINDEFORS, N
通讯作者：
LINDEFORS, N
影响因子：
3.3
作者：
ANDREW, RD;MACVICAR, BA
通讯作者：
MACVICAR, BA
影响因子：
1.7
作者：
BAKAY L
通讯作者：
BAKAY L