Intracerebral microdialysis: I. Experimental studies of diffusion kinetics

Intracerebral microdialysis is a brain perfusion technique in which a tubular, semipermeable membrane perfused with a physiological solution is implanted into a selected brain region. Molecules in the extracellular space diffuse into the perfusate and may be recovered and their concentration determined. Hence, the level of substances such as neurotransmitters may be monitored, and the response to different treatments may be studied. The technique also allows for administration of substances locally to the region of the brain surrounding the perfused tubular membrane. Basic principles of the microdialysis technique are described, and the results from methodological experiments are examined. It is concluded that there is a direct linear relation between the concentration of a molecule in the medium surrounding the dialysis membrane and the concentration measured in the collected perfusate. Relative changes of molecular concentration in brain extracellular space may be calculated even when the molecular diffusion rate is unknown. In addition, a method is presented for calculating the real concentration of a substance in the extracellular space from its concentration in the perfusate. Applied in striatum of rat brain using microdialysis in vivo, the average extracellular concentration of the following substances is estimated to be: substance P, 0.9 nM; dopamine, 1 microM; and dihydroxyphenylacetic acid, 0.05 mM.