Quantitative Examination of Tissue Concentration Profiles Associated with Microdialysis

Abstract

Spatial solute concentration profiles resulting from in vivo microdialysis were measured in rat caudate-putamen by quantitative autoradiography. Radiolabeled sucrose was included in the dialysate, and the tissue concentration profile measured after infusions of 14 min and 61.5 min in an acute preparation. In addition, the changes in sucrose extraction fraction over time were followed in vivo and in a simple in vitro system consisting of 0.5% agarose. These experimental results were then compared with mathematical simulations of microdialysis in vitro and in vivo. Simulations of in vitro microdialysis agreed well with experimental results. In vivo, the autoradiograms of the tissue concentration profiles showed clear evidence of substantial differences between 14 and 61.5 min, even though the change in extraction fraction was relatively small over that period. Comparison with simulated results showed that the model substantially underpredicted the observed extraction fraction and overall amount of sucrose in the tissue. A sensitivity analysis of the various model parameters suggested a tissue extracellular volume fraction of approximately 40% following probe implantation. We conclude that the injury from probe insertion initially causes disruption of the blood-brain barrier in the vicinity of the probe, and this disruption leads to an influx of water and plasma constituents, causing a vasogenic edema.

A model for simulation and patient-specific visualization of the tissue volume of influence during brain microdialysis

“…It is therefore clinically beneficial to visualize the r TVImax and associated TVI max for a catheter when using brain microdialysis, to determine whether the measurement sites are correct and comparable between patients when interpreting physiological data. The extension of the TVI max is also reasonable in comparison to previous studies, predicting that the microdialysis penetration depth for similar substances would be within the millimeter range [27][28][29].…”

Anin vitroblood–brain barrier model: Cocultures between endothelial cells and organotypic brain slice cultures

“…Intracerebral microdialysis is an in vivo technique by which concentrations of small endogenous compounds can be monitored dynamically (71,72). More recently, applications in the field of pharmacokinetics have been reported (73)(74)(75), where microdialysis has appeared as a powerful tool to investigate BBB transport (76,77). We previously described an application of the microdialysis technique for monitoring changes in Glu release on hippocampal organotypic slice cultures (33).…”

Microdialysis as an Important Technique in Systems Pharmacology—a Historical and Methodological Review

“…1. Number of publications per year on Bmicrodialysis,^of which 71% are brain microdialysis studies and 24% are microdialysis studies in humans, according to information on PubMed concentrations in the probe and the surrounding tissue, and that in vitro recovery is not sufficient for in vivo estimations of extracellular concentrations (42,(44)(45)(46)(47)61). This is due to the difference in movement of molecules in the tissue vs in a buffer solution (Fig.…”

“…Early methodological papers presented important principles of microdialysis, including solute exchange across the semi-permeable membrane, and highlighting the role of quantitative measurements as well as time aspects of the measurements (41)(42)(43)(44)(45)(46)(47). Theoretical aspects have been pursued further, all relying on the early papers (15,(48)(49)(50)(51)(52)(53).…”