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Principle of microdialysis

Monitoring in vivo - representative samples of all soluble molecules in the ECF
- high sensitivity
- effects of drugs on basal neurotransmitter levels

Microdialysis is a minimally invasive technique allowing in vivo sampling of molecules transported into, or generated within the extracellular space of principally any tissue or organ in the body and also for sampling the body fluids such as blood or CSF. Microdialysis in combination with a suitable detection technique allows monitoring of time-dependent changes in local tissue chemistry, for example neurotransmitter release and reuptake, drug delivery or energy metabolism in a particular brain area. The unsurpassed feature of in vivo microdialysis is its capability to provide information on basal, non-stimulated levels of extracellular neurotransmitters, as well as, on pharmacologically or physiologically stimulated release. This offers a unique opportunity to examine the role of various receptor subtypes in tonic and phasic regulation of neurotransmitter release and metabolism in neuroanatomically relevant brain structures.

Microdialysis technique provides the most comprehensive information on dynamic changes of molecules involved in intercellular communication and metabolism at an integrative (whole body) level, preserving the overall physiological and behavioral functions.

Several independent techniques have demonstrated that the molecular movement within the extracellular space is driven predominantly by diffusion. In an analogous way, the driving force of microdialysis sampling is the diffusion of molecules across the concentration gradients existing between the two compartments separated by the membrane: the tissue/extracellular space compartment and the perfusion fluid inside the probe as the second compartment.  Thus, the molecules can move in both directions, which allows simultaneous recovery of endogenous compounds released into the brain microenvironment and at the same time, drugs can be delivered locally through the probe into the sampled area.

Microdialysis can be used for monitoring the kinetics of drug distribution and clearance in different organs, which for the brain studies is of particular interest since it allows evaluating the ability of drugs to penetrate through the blood-brain barrier.



The principle of microdialysis sampling and the origin of molecules released into the brain microenvironment. The molecular movement of substances present in the extracellular fluid is driven predominantly by diffusion. Depending on the concentration gradients across the membrane of the microdialysis probe, the molecules can move in both directions, which allows simultaneous recovery of endogenous compounds and at the same time, drugs can be added to the perfusion medium and delivered locally into the same brain structure.

The most interesting and thoroughly studied molecules are (depicted by numbers): 1,2,3 - neurotransmitters, neuromodulators and neuropeptides; 3,4 - the neuron-glia interactions, glutamate and GABA, large molecules such as interleukins and trophic factors; 5 - second messengers cAMP, cGMP or arachidonic acid metabolites; 6 - molecules transported from blood capillaries - glucose, nutrients, drugs; 7 - neuro-vascular communication - NO; 8 - molecules transported from or into the CSF.
Adopted from: Kehr J, Yoshitake T (2006) Monitoring brain chemical signals by microdialysis. In: Encyclopedia of Sensors (Eds CA Grimes, EC Dickey and MV Pishko) American Scientific Publishers, USA, pp 287-312.

References
Kehr J (1999) Monitoring chemistry of brain microenvironment: biosensors, microdialysis and related techniques, Chapter 41.  In: Modern techniques in neuroscience research (Eds U Windhorst and H Johansson) Springer-Verlag GmbH, Heidelberg, 1149-1198.
Kehr J, Yoshitake T (2006) Monitoring brain chemical signals by microdialysis. In: Encyclopedia of Sensors, Vol. 6. (Eds CA Grimes, EC Dickey and MV Pishko) American Scientific Publishers, USA, pp 287-312.
Kehr J (2007) New methodological aspects of microdialysis. In: Handbook of microdialysis: Methods, Applications and Perspectives (Eds BHC Westerink and T Cremers) Elsevier, The Netherlands, pp 111-129.