1One reviewer kindly reminded us that our fitting results in vivo would be more accurate if the Dm was also temperature-adjusted. We estimated that the Dm becomes 2.0 × 10−6 cm2 s−1 at 37°C, a 33% increase. We believe that this change in Dm would not significantly alter the fitting result in brain because the membrane resistance measured with 3H-mannitol is much smaller than the tissue resistance.
Quantitative dual-probe microdialysis: mathematical model and analysis
Article first published online: 25 MAR 2002
Journal of Neurochemistry
Volume 81, Issue 1, pages 94–107, April 2002
How to Cite
Chen, K. C., Höistad, M., Kehr, J., Fuxe, K. and Nicholson, C. (2002), Quantitative dual-probe microdialysis: mathematical model and analysis. Journal of Neurochemistry, 81: 94–107. doi: 10.1046/j.1471-4159.2002.00792.x
- Issue published online: 25 MAR 2002
- Article first published online: 25 MAR 2002
- Received July 25, 2001; revised manuscript received December 18, 2001; accepted December 21, 2001.
- extracellular diffusion;
- volume transmission
Steady-state microdialysis is a widely used technique to monitor the concentration changes and distributions of substances in tissues. To obtain more information about brain tissue properties from microdialysis, a dual-probe approach was applied to infuse and sample the radiotracer, [3H]mannitol, simultaneously both in agar gel and in the rat striatum. Because the molecules released by one probe and collected by the other must diffuse through the interstitial space, the concentration profile exhibits dynamic behavior that permits the assessment of the diffusion characteristics in the brain extracellular space and the clearance characteristics. In this paper a mathematical model for dual-probe microdialysis was developed to study brain interstitial diffusion and clearance processes. Theoretical expressions for the spatial distribution of the infused tracer in the brain extracellular space and the temporal concentration at the probe outlet were derived. A fitting program was developed using the simplex algorithm, which finds local minima of the standard deviations between experiments and theory by adjusting the relevant parameters. The theoretical curves accurately fitted the experimental data and generated realistic diffusion parameters, implying that the mathematical model is capable of predicting the interstitial diffusion behavior of [3H]mannitol and that it will be a valuable quantitative tool in dual-probe microdialysis.