Skip to main content

Advertisement

Log in

Microdialysis of large molecules

  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

Microdialysis has been used in many tissues, including skin, brain, adipose tissue, muscle, kidney, and gastrointestinal tract, to recover low-molecular mass endogenous mediators, metabolites, and xenobiotics from the interstitial space. Recently, molecules of larger molecular mass, such as plasma proteins, cytokines, growth factors, and neuropeptides, have also been recovered successfully using largerpore membranes. Microdialysis recovery of large molecules offers the opportunity to identify patterns of protein expression in a variety of tissue spaces and to evaluate clinically useful biomarkers of disease. From this may develop a better understanding of the disease process and its diagnosis and more targeted approaches to therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bito L, Davson H, Levi EM, Murray M, Snider N. The concentration of free amino acids and other electrolytes in cerebrospinal fluid, in vivo dialysate of brain, and blood plasma of the dog.J Neurochem. 1966;13:1057–1067.

    Article  PubMed  CAS  Google Scholar 

  2. Petersen LJ, Church MK, Skov PS. Histamine is released in the wheal but not the flare following challenge of human skin in vivo: a microdialysis study.Clin Exp Allergy. 1997;27:284–295.

    Article  PubMed  CAS  Google Scholar 

  3. Andersson T, Wardell K, Anderson C. Human in vivo cutaneous microdialysis: estimation of histamine release in cold urticaria.Acta Derm Venereol. 1995;75:343–347.

    PubMed  CAS  Google Scholar 

  4. Krogstad AL, Jansson PA, Gisslen P, Lonnroth P. Microdialysis methodology for the measurement of dermal interstitial fluid in hum ans.Br J Dermatol. 1996;134:1005–1012.

    Article  PubMed  CAS  Google Scholar 

  5. Kellogg DL, Jr, Crandall CG, Liu Y, Charkoudian N, Johnson JM. Nitric oxide and cutaneous active vasodilation during heat stress in humans.J Appl Physiol. 1998;85:824–829.

    PubMed  CAS  Google Scholar 

  6. Klede M, Clough G, Lischetzki G, Schmelz M. The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester on neuropeptide-induced vasodilation and protein extravasation in human skin.J Vasc Res. 2003;40:105–114.

    Article  PubMed  CAS  Google Scholar 

  7. Clough GF. Role of nitric oxide in the regulation of microvascular perfusion in human skin in vivo.J Physiol. 1999;516:549–557.

    Article  PubMed  CAS  Google Scholar 

  8. Rhodes LE, Belgi G, Parslew R, McLoughlin L, Clough GF, Friedmann PS. Ultraviolet-B-induced erythema is mediated by nitric oxide and prostaglandin E2 in combination.J Invest Dermatol. 2001;117:880–885.

    Article  PubMed  CAS  Google Scholar 

  9. Sun L, Stenken JA. Improving microdialysis extraction efficiency of lipophilic eicosanoids.J Pharm Biomed Anal. 2003;33:1059–1071.

    Article  PubMed  CAS  Google Scholar 

  10. Lindberger M, Tomson T, Wallstedt L, Stahle L. Distribution of valproate to subdural cerebrospinal fluid, subcutaneous extracellular fluid, and plasma in humans: a microdialysis study.Epilepsia. 2001;42:256–261.

    Article  PubMed  CAS  Google Scholar 

  11. Newman JM, Di Maria CA, Rattigan S, Clark MG. Nutritive blood flow affects microdialysis O/I ratio for [(14)C]ethanol and (3)H(2)O in perfused rat hindlimb.Am J Physiol Heart Circ Physiol. 2001;281:H2731-H2737.

    PubMed  CAS  Google Scholar 

  12. Tegeder I, Muth-Selbach U, Lotsch J, et al. Application of microdialysis for the determination of muscle and subcutaneous tissue concentrations after oral and topical ibuprofen administration.Clin Pharmacol Ther. 1999;65:357–368.

    Article  PubMed  CAS  Google Scholar 

  13. Iversen HH, Celsing F, Leone AM, Gustafsson LE, Wiklund NP. Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis.Br J Pharmacol. 1997;120:702–706.

    Article  PubMed  CAS  Google Scholar 

  14. Schmelz M, Luz O, Averbeck B, Bickel A. Plasma extravasation and neuropeptide release in human skin as measured by intradermal microdialysis.Neurosci Lett. 1997;230:117–120.

    Article  PubMed  CAS  Google Scholar 

  15. Winter CD, Iannotti F, Pringle AK, Trikkas C, Clough GF, Church MK. A microdialysis method for the recovery of IL-1beta, IL-6 and nerve growth factor from human brain in vivo.J Neurosci Methods. 2002;119:45–50.

    Article  PubMed  CAS  Google Scholar 

  16. Winter CD, Pringle AK, Clough GF, Church MK. Raised parenchymal interleukin-6 levels correlate with improved outcome after traumatic brain injury.Brain. 2004;127:315–320.

    Article  PubMed  Google Scholar 

  17. Dabrosin C. Variability of vascular endothelial growth factor in normal human breast tissue in vivo during the menstrual cycle.J Clin Endocrinol Metab. 2003;88:2695–2698.

    Article  PubMed  CAS  Google Scholar 

  18. Maurer MH, Berger C, Wolf M, et al. The proteome of human brain microdialysate.Proteome Sci. 2003;1:7.

    Article  PubMed  Google Scholar 

  19. Ernberg MM, Alstergren PJ. Microdialysis of neuropeptide Y in human muscle tissue.J Neurosci Methods. 2004;132:185–190.

    Article  PubMed  CAS  Google Scholar 

  20. Haskins WE, Watson CJ, Cellar NA, Powell DH, Kennedy RT. Discovery and neurochemical screening of peptides in brain extracellular fluid by chemical analysis of in vivo microdialysis samples.Anal Chem. 2004;76:5523–5533.

    Article  PubMed  CAS  Google Scholar 

  21. Woodroofe MN, Sarna GS, Wadhwa M, et al. Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production.J Neuroimmunol. 1991;33:227–236.

    Article  PubMed  CAS  Google Scholar 

  22. Sjogren F, Svensson C, Anderson C. Technical prerequisites for in vivo microdialysis determination of interleukin-6 in human dermis.Br J Dermatol. 2002;146:375–382.

    Article  PubMed  CAS  Google Scholar 

  23. Fellows PJ, Noble MR, Clough GF. Effect of perfusion rate on the recovery of albumin by microdialysis.J Vasc Res. 2003;40:304.

    Google Scholar 

  24. Riese J, Boecker S, Hohenberger W, Klein P, Haupt W. Microdialysis: a new technique to monitor perioperative human peritoneal mediator production.Surg Infect (Larchmt). 2003;4:11–15.

    Article  Google Scholar 

  25. Dabrosin C. Technical aspects of microdialysis of human breast.Scand J Clin Lab Invest. 2001;61:269–272.

    Article  PubMed  CAS  Google Scholar 

  26. Brown SA, Mayberry AJ, Mathy JA, Phillips TM, Klitzman B, Levin LS. The effect of muscle flap transposition to the fracture site on TNFalpha levels during fracture healing.Plast Reconstr Surg. 2000;105:991–998.

    Article  PubMed  CAS  Google Scholar 

  27. Licht P, Losch A, Dittrich R, Neuwinger J, Siebzehnrubl E, Wildt L. Novel insights into human endometrial paracrinology and embryo-maternal communication by intrauterine microdialysis.Hum Reprod Update. 1998;4:532–538.

    Article  PubMed  CAS  Google Scholar 

  28. Trickler WJ, Miller DW. Use of osmotic agents in microdialysis studies to improve the recovery of macromolecules.J Pharm Sci. 2003;92:1419–1427.

    Article  PubMed  CAS  Google Scholar 

  29. Ao X, Sellati TJ, Stenken JA. Enhanced microdialysis relative recovery of inflammatory cytokines using antibody-coated microspheres analyzed by flow cytometry.Anal Chem. 2004;76:3777–3784.

    Article  PubMed  CAS  Google Scholar 

  30. Schutte RJ, Oshodi SA, Reichert WM. In vitro characterization of microdialysis sampling of macromolecules.Anal Chem. 2004;76:6058–6063.

    Article  PubMed  CAS  Google Scholar 

  31. Clough GF, Boutsiouki P, Church MK, Michel CC. Effects of blood flow on the in vivo recovery of a small diffusible molecule by microdialysis in human skin.J Pharmacol Exp Ther. 2003;302:681–686.

    Article  CAS  Google Scholar 

  32. Wiig H, Sibley L, DeCarlo M, Renkin EM. Sampling interstitial fluid from rat skeletal muscles by intermuscular wicks.Am J Physiol. 1991;261:H155-H165.

    PubMed  CAS  Google Scholar 

  33. Haaverstad R, Romslo I, Larsen S, Myhre HO. Protein concentration of subcutaneous interstitial fluid in the human leg: a comparison between the wick technique and the blister suction technique.Int J Microcirc Clin Exp. 1996;16:111–117.

    PubMed  CAS  Google Scholar 

  34. Rutili G, Arfors KE. Protein concentration in interstitial and lymphatic fluids from the subcutaneous tissue.Acta Physiol Scand. 1977;99:1–8.

    Article  PubMed  CAS  Google Scholar 

  35. Hamrin K, Rosdahl H, Ungerstedt U, Henriksson J. Microdialysis in human skeletal muscle: effects of adding a colloid to the perfusate.J Appl Physiol. 2002;92:385–393.

    Article  PubMed  CAS  Google Scholar 

  36. Sun H, Bungay PM, Elmquist WF. Effect of capillary efflux transport inhibition on the determination of probe recovery during in vivo microdialysis in the brain.J Pharmacol Exp Ther. 2001;297:991–1000.

    PubMed  CAS  Google Scholar 

  37. Church MK, Griffiths TJ, Jeffery S, et al. Are cysteinyl leukotrienes involved in allergic responses in human skin?.Clin Exp Allergy. 2002;32:1013–1019.

    Article  PubMed  CAS  Google Scholar 

  38. Winter CD, Iannotti F, Pringle AK, Trikkas C, Clough GF, Church MK. A microdialysis method for the recovery of IL-1beta, IL-6 and nerve growth factor from human brain in vivo.J Neurosci Methods. 2002;119:45–50.

    Article  PubMed  CAS  Google Scholar 

  39. Ao X, Stenken JA. Water-soluble cyclodextrin polymers for enhanced relative recovery of hydrophobic analytes during microdialysis sampling.Analyst. 2003;128:1143–1149.

    Article  PubMed  CAS  Google Scholar 

  40. Kjellstrom S, Emneus J, Laurell T, Heintz L, Marko-Varga G. On-line coupling of microdialysis sampling with liquid chromatography for the determination of peptide and non-peptide leukotrienes.J Chromatogr A. 1998;823:489–496.

    Article  PubMed  CAS  Google Scholar 

  41. Davies MI, Cooper JD, Desmond SS, Lunte CE, Lunte SM. Analytical considerations for microdialysis sampling.Adv Drug Deliv Rev. 2000;45:169–188.

    Article  PubMed  CAS  Google Scholar 

  42. Lunte SM, Lunte CE. Microdialysis sampling for pharmacological studies: HPLC and CE analysis.Adv Chromatogr. 1996;36:383–432.

    PubMed  CAS  Google Scholar 

  43. Graham DR, Elliott ST, Van Eyk JE. Broad-based proteomic strategies: a practical guide to proteomics and functional screening.J Physiol. 2005;563:1–9.

    Article  PubMed  CAS  Google Scholar 

  44. Kellar KL, Douglass JP. Multiplexed microsphere-based flow cytometric immunoassays for human cytokines.J Immunol Methods. 2003;279:277–285.

    Article  PubMed  CAS  Google Scholar 

  45. Anderson L. Candidate-based proteomics in the search for biomarkers of cardiovascular disease.J Physiol. 2005;563:23–60.

    Article  PubMed  CAS  Google Scholar 

  46. Rohlff C, Hollis K. Modern proteomic strategies in the study of complex neuropsychiatric disorders.Biol Psychiatry. 2003;53:847–853.

    Article  PubMed  CAS  Google Scholar 

  47. O’Riordan E, Orlova TN, Mei JJ, et al. Bioinformatic analysis of the urine proteome of acute allograft rejection.J Am Soc Nephrol. 2004;15:3240–3248.

    Article  PubMed  Google Scholar 

  48. Richter R, Schulz-Knappe P, Schrader M, et al. Composition of the peptide fraction in human blood plasma: database of circulating human peptides.J Chromatogr B Biomed Sci Appl. 1999;726:25–35.

    Article  PubMed  CAS  Google Scholar 

  49. Tolson J, Bogumil R, Brunst E, et al. Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients.Lab Invest. 2004;84:845–856.

    Article  PubMed  CAS  Google Scholar 

  50. Schmid P. Quantitation of specific proteins in blister fluid.J Invest Dermatol. 1970;55:244–248.

    Article  PubMed  CAS  Google Scholar 

  51. Nedrebo T, Reed RK, Jonsson R, Berg A, Wiig H. Differential cytokine response in interstitial fluid in skin and serum during experimental inflammation in rats.J Physiol. 2004;556:193–202.

    Article  PubMed  CAS  Google Scholar 

  52. Iversen VV, Bronstad A, Gjerde EA, Reed RK. Continuous measurements of plasma protein extravasation with microdialysis after various inflammatory challenges in rat and mouse skin.Am J Physiol Heart Circ Physiol. 2004;286:H108-H112.

    Article  PubMed  CAS  Google Scholar 

  53. Schmelz M, Petersen LJ. Neurogenic inflammation in human and rodent skin.News Physiol Sci. 2001;16:33–37.

    PubMed  CAS  Google Scholar 

  54. Weidner C, Klede M, Rukwied R, et al. Acute effects of substance P and calcitonin gene-related peptide in human skin: a microdialysis study.J Invest Dermatol. 2000;115:1015–1020.

    Article  PubMed  CAS  Google Scholar 

  55. Krogstad AL, Lonnroth P, Larson G, Wallin BG. Increased interstitial histamine concentration in the psoriatic plaque.J Invest Dermatol. 1997;109:632–635.

    Article  PubMed  CAS  Google Scholar 

  56. Garvin S, Dabrosin C. Tamoxifen inhibits secretion of vascular endothelial growth factor in breast cancer in vivo.Cancer Res. 2003;63:8742–8748.

    PubMed  CAS  Google Scholar 

  57. Simonsen L, Holstein P, Larsen K, Bulow J. Glucose metabolism in chronic diabetic foot ulcers measured in vivo using microdialysis.Clin Physiol. 1998;18:355–359.

    Article  PubMed  CAS  Google Scholar 

  58. Clough GF, Noble MR. Microdialysis: a model for studying chronic wounds.Int J Low Extrem Wounds. 2003;2:233–239.

    Article  PubMed  Google Scholar 

  59. Westerink BH, De Vries JB. A method to evaluate the diffusion rate of drugs from a microdialysis probe through brain tissue.J Neurosci Methods. 2001;109:53–58.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Geraldine F. Clough.

Additional information

Published: October 26, 2005

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clough, G.F. Microdialysis of large molecules. AAPS J 7, 69 (2005). https://doi.org/10.1208/aapsj070369

Download citation

  • Received:

  • Accepted:

  • DOI: https://doi.org/10.1208/aapsj070369

Keywords

Navigation