Mathematical Model of Hippocampal Microdialysis: Validation of in vivo Methodology

TL;DR

This paper develops and validates a mathematical model of hippocampal microdialysis, confirming that steady-state conditions are quickly achieved, thus supporting the accuracy of in vivo neurochemical measurements using the zero-net-flux method.

Contribution

A first-principles model of fluid flow and analyte diffusion was created and validated, confirming the rapid attainment of steady-state in hippocampal microdialysis.

Findings

Model accurately predicts in vivo results

Steady-state achieved within 1-2 minutes

Supports validity of zero-net-flux method

Abstract

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.