Microdialysis update: optimizing the advantages.

Microdialysis was introduced in the early 1970s as a method to measure dynamic release of substances in the brain (see Tossman & Ungerstedt, 1986). The technique has been refined over the past three decades due to the development of new materials for dialysis membranes and commercial availability of smaller, more consistently fabricated probes. A typical microdialysis probe consists of rigid metal concentric tubing with a semipermeable region at the tip (Fig. 1). Molecules of restricted size passively diffuse from the brain through the dialysis membrane into an infusion solution which is then directed out of the brain and collected in tubes for serial analysis of substance content. Probes are inserted into the brain region of interest, typically making lesions during their travel through the brain and at the sampling site. Once the trauma of insertion subsides, usually after an hour or so, probes collect substances released from axons projecting to dendrites and cell bodies of the targeted area. Substances surrounding the semipermeable region of the probe passively diffuse down a concentration gradient into the solution infused through the probe. Substance recovery from the brain decreases exponentially with faster infusion rates. A high precision infusion pump is critical for maintaining constant flow through the probes to ensure that altered substance content in the dialysates reflects changes in release by the brain and not variable diffusion gradients resulting from sporadic changes in flow rates through the probes. High performance liquid chromatography (HPLC) is commonly used to measure target substances in the dialysates, but other methods such as radioimmunoassay may be employed. The development of microbore columns for HPLC (Durkin et al. 1985) and their commercial availability by the mid 1990s has made it possible to accurately measure smaller amounts of substances in the dialysates.