Journal of Molecular Medicine

, Volume 74, Issue 9, pp 523–526 | Cite as

Microdialysis: a way to study in vivo release of neurotrophic bioactivity: a critical summary

  • C. Humpel
  • T. Ebendal
  • L. Olson


Microdialysis has been proven to be a valuable tool to study in vivo release of various neurotransmitters in the rat brain. Recently we demonstrated for the first time the release of neurotrophic bioactivity in the brains of awake rats. Neurotrophic factors, however, exist in extremely low concentrations in the brain compared to neurotransmitters, rendering their detection particularly difficult. This review summarizes knowledge about the use of microdialysis for the detection of neurotrophic bioactivity, its limits, and its problems.

Key words

In vivo Microdialysis Release Secretion Trophic factors 



Brain-derived neurotrophic factor


Enzyme immunoassay


Nerve growth factor




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  1. 1.
    Zetterströom T, Sharp T, Marsden C and Ungerstedt U (1983) In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine J Neurochem 41:1769–1773Google Scholar
  2. 2.
    Di Chiara G (1990) In vivo brain dialysis of neurotransmitters. Trends Pharmacol Sci 11:116–121Google Scholar
  3. 3.
    Kalen P, Nilsson OG, Cenci MA, Rosengren E, Lindvall O, Björklund A (1990) Intracerebral microdialysis as a tool to monitor transmitter release from grafted cholinergic and monoaminergic neurons. J Neurosci Methods 34:107–115Google Scholar
  4. 4.
    Kendrick KM (1989) Use of microdialysis in neuroendocrinology. Methods Enzymol 168:182–205Google Scholar
  5. 5.
    Levine JE, Powell KD (1989) Microdialysis for measurement of neuroendocrine peptides. Methods Enzymol 168:166–181Google Scholar
  6. 6.
    Benveniste H (1989) Brain microdialysis. J Neurochem 52: 1667–1679Google Scholar
  7. 7.
    Humpel C, Lindqvist E, Söderström S, Kylberg A, Ebendal T, Olson L (1995) Monitoring release of neurotrophic activity in the brains of awake rats. Science 269:552–554Google Scholar
  8. 8.
    Ruggeri M, Zoli M, Grimaldi R, Ungerstedt U, Eliasson A, Agnati LF, Fuxe K (1990) Aspects ofneural plasticity in the central nervous system. III. Methodological studies on the microdialysis technique. Neurochem Int 16:427–435Google Scholar
  9. 9.
    Benveniste H, Diemer NH (1987) Cellular reactions to implantation of a microdialysis tube in the rat hippocampus. ActaNeuropathol 74:234–238Google Scholar
  10. 10.
    Shuaib A, Xu K, Crain B, Siren AL, Feuerstein G, Hallenbeck J, Dais JNv (1990) Assessment of damage from implantation of microdialysis probes in the rat hippocampus with silver degeneration staining. Neurosci Lett 112:149–154Google Scholar
  11. 11.
    Benveniste H, Drejer J, Schousboe A, Diemer N (1987) Regional cerebral glucose phosphorylation and blood flow after insertion of a microdialysis fiber through the dorsal hippocampus in the rat. J Neurochem 49 49:729–73Google Scholar
  12. 12.
    Nieto-Sampedro M, Lewis ER, Cotman CW, Manthorpe M, Skaper SD, Barbin G, Longo FM, Varon S (1982) Brain injury causes a time-dependent increase in neuronotrophic activity at the lesion side. Science 217:860–861Google Scholar
  13. 13.
    Finklestein SP, Apostolides PJ, Caday CG, Prosser J, Philips MF, Klagsbrun M (1988) Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds. Brain Res 460:253–259Google Scholar
  14. 14.
    Humpel C, Chadi G, Lippoldt A, Ganten D, Fuxe K, Olson L (1994) Increase of basic fibroblast growth factor (bFGF, FGF-2) messenger RNA and protein following implantation of a microdialysis probe into rat hippocampus. Exp Brain Res 98:229–237Google Scholar
  15. 15.
    Ballarin M, Ernfors P, Lindefors N, Persson H (1991) Hippocampal damage and kainic acid injection induce a rapid increase in mRNA for BDNF and NGF in the rat brain. Exp Neurol 114:35–43Google Scholar
  16. 16.
    Gall CM (1992) Regulation of brain neurotrophin expression by physiological activity. Trends Pharmacol Sci 13:401–403Google Scholar
  17. 17.
    Lindholm D, Castren E, Berzaghi M, Blöchl A, Thoenen H (1994) Activity-dependent and hormonal regulation of neurotrophin mRNA levels in the brain. Implications for neuronal plasticity. J Neurobiol 25:1362–1372Google Scholar
  18. 18.
    Lindvall O, Kokaia Z, Bengzon J, Elmer E, Kokaia M (1994) Neurotrophins and brain insults. Trends Neurosci 17:490–496Google Scholar
  19. 19.
    Ebendal T (1989) Use of collagen gels to bioassay nerve growth factor activity. In: Rush RA et al. (eds) Methods in the neurosciences: nerve growth factors, vol 12. John Wiley & Sons, New York, pp 81–94Google Scholar
  20. 20.
    Blöchl A, Thoenen H (1995) Characterization of nerve growth factor (NGF) release from hippocampal neurons: evidence for a constitutive and an unconventional sodium-dependent regulated pathway. Eur J Neurosci 7:1220–1228Google Scholar
  21. 21.
    Lindsay RM (1994) Neurotrophic growth factors and neurode-generative diseases: therapeutic potential of the neurotrophins and ciliary neurotrophic factor. Neurobiol Aging 15:249–251Google Scholar
  22. 22.
    Lindsay RM, Wiegand SJ Altar CA, DiStefano PS (1994) Neurotrophic factors: from molecule to man. Trends Neurosci 17:182–190Google Scholar
  23. 23.
    Hefti F (1994) Neurotrophic factor therapy for nervous system degenerative diseases. J Neurobiol 25:1418–1435Google Scholar
  24. 24.
    Tomac A, Lindqvist E, Lin LFH, Ögren SO, Young D, Hoffer BJ, Olson L (1995) Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373:335–339CrossRefPubMedGoogle Scholar
  25. 25.
    Seiger A, Nordberg A, Von Holst H, Böckman L, Ebendal T, Alafuzoff I, Amberla K, Hartvig P, Herlitz A, Lilja A, Lundqvist H, Langström B, Meyerson B, Persson A, Viitanen M, Winblad B, Olson L (1993) Intracranial infusion of purifiednerve growth factor to an Alzheimer patient: the first attempt of a possible future treatment strategy. Behav Brain Res 57: 255–261Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • C. Humpel
    • 1
  • T. Ebendal
    • 2
  • L. Olson
    • 3
  1. 1.Neurochemistry Unit, Department of PsychiatryInnsbruckAustria
  2. 2.Department of Developmental NeurosciencesUniversity of UppsalaSweden
  3. 3.Department of NeuroscienceKarolinska InstituteStockholmSweden

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