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arXiv 2011.06662q-bio.QMq-bio.NC
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海马微透析的数学模型:体内方法学验证

Mathematical Model of Hippocampal Microdialysis: Validation of in vivo Methodology

Damon Vinciguerra, Margot Vigeant, Ewan C. McNay

摘要:

微透析是一种成熟的小分子体内神经化学测量方法,植入同心设计的探针提供最小的组织损伤和良好的时间和空间分辨率。然而,绝大多数的测量不允许灌注液与大脑达到平衡,因此必须使用诸如零净流量的样本浓度校正的推断方法来确定实际的脑细胞外液葡萄糖浓度。为了使这些方法有效,需要脑内感兴趣的分析物的稳态转移,但这种情况以前没有得到证实。第一原理数学模型的流体流动和分析物扩散周围植入的微透析探头开发和实施,以验证零净通量的方法,使用测量细胞外脑葡萄糖水平作为一个良好的探索的例子系统,对该模型进行比较。该模型的结果准确地再现和预测了体内实验的结果。重要的是,该模型预测植入的探针与周围细胞外液达到稳态平衡的时间大约为一到两分钟,这支持了该技术用于定量测量体内神经化学的有效性。

英文摘要:

Microdialysis is a well-established method for in vivo neurochemical measurements of small molecules, with implanted concentric-design probes offering minimized tissue damage and good temporal and spatial resolution. However, the large majority of measurements do not allow the perfusate to reach equilibrium with the brain, so that inferential methods of sample concentration correction such as zero-net-flux must be used to determine actual brain extracellular fluid glucose concentrations. In order for such methods to be valid, steady-state transfer of the analyte of interest within the brain is required, but this situation has not previously been confirmed. A first-principles mathematical model of fluid flow and analyte diffusion around an implanted microdialysis probe was developed and implemented in COMSOL in order to validate the zero-net-flux approach, using measurement of extracellular brain glucose levels as a well-explored example system against which to compare the model. Results from the model accurately reproduced and predicted results from in vivo experiments. Importantly, the model predicts that the time for an implanted probe to achieve steady-state equilibrium with the surrounding extracellular fluid is on the order of one to two minutes, supporting the validity of this technique for quantitative measurement of in vivo neurochemistry.

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