论文标题

海马微透析的数学模型:体内方法的验证

Mathematical Model of Hippocampal Microdialysis: Validation of in vivo Methodology

论文作者

Vinciguerra, Damon, Vigeant, Margot, McNay, Ewan C.

论文摘要

微透析是一种完善的方法,用于对小分子进行体内神经化学测量,其植入同心设计探针可提供最小化的组织损伤以及良好的时间和空间分辨率。但是,绝大多数测量不允许灌注液与大脑达到平衡,因此必须使用样品浓度校正的推论方法,例如零网络液液,以确定实际的脑外细胞外液葡萄糖浓度。为了使此类方法具有有效,需要大脑中感兴趣的分析物的稳态转移,但是以前尚未确认这种情况。开发和实现了植入的微透析探针围绕流体流量和分析物扩散的第一原理数学模型,并在COMSOL中实现,以验证零NET-FLUX方法,使用细胞外脑葡萄糖水平的测量作为一个很好的示例系统,可以与该模型进行比较。该模型的结果准确地复制并预测了体内实验的结果。重要的是,该模型预测,植入探针实现稳态平衡的时间与周围的细胞外流体达到一到两分钟的阶段,这支持了该技术的有效性,以定量体内神经化学的定量测量。

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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