Skip to main content

Reparative Strategies in the Brain: Treatment Strategies Based on Trophic Factors and Cell Transfer Techniques

  • Conference paper
Advances in Stereotactic and Functional Neurosurgery 10

Part of the book series: Acta Neurochirurgica ((STEREOTACTIC,volume 58))

  • 108 Accesses

Summary

Three reparative strategies based on transfer of genes, molecules, or cells to the central nervous system are reviewed. When neurons are already lost, they can sometimes be replaced by transfer to the target area of neurons or other cells compensating for the lost functions. This technique is undergoing clinical trials in Parkinson’s disease. Before neurons have died, it may be possible to prevent “stressed” neurons from dying, and stimulate nerve terminal ramifications from remaining neurons using treatment with neurotrophic factors. Such approaches, with an emphasis on the NGF family of neurotrophins and their receptors, are reviewed. Finally, advances of molecular biology techniques suggest that it should be possible to transfer genes directly into non-dividing cells of the central nervous system. The three different approaches all aim at long-lasting counteractive and reparative measures in the central nervous system. It is predicted that they have general applicability, and may become important not only in neurodegenerative diseases, but also in other common afflictions of the nervous system such as ischaemia, stroke and injury.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barde YA (1990) The nerve growth factor family. Prog Growth Factor Res 2: 237–248

    Article  PubMed  CAS  Google Scholar 

  2. Bothwell M (1991) Keeping track of neurotrophin receptors. Cell 65: 915–918

    Article  PubMed  CAS  Google Scholar 

  3. David S, Aguayo AJ (1981) Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science 214: 931–93

    Article  PubMed  CAS  Google Scholar 

  4. Ebendal T (1992) Function and evolution in the NGF family and its receptors. J Neurosci Res 32: 461–470

    Article  PubMed  CAS  Google Scholar 

  5. Ernfors P, Ebendal T, Olson L, Mouton P, Strömberg I, Persson H (1989) A cell line producing recombinant nerve growth factor evokes growth responses in intrinsic and grafted central cholinergic neurons. Proc Natl Acad Sci USA 86: 4756–4760

    Article  PubMed  CAS  Google Scholar 

  6. Freed CR, Breeze RE, Roxenberg NL, Schneck SA, Kriek E, Qi JX, Lone T, Zhang YB, Snyder JA, Wells TH, Ramig LO, Thompson L, Mazziotta JC, Huang SC, Grafton ST, Brooks D, Sawle G, Schroter G, Ansari AA (1992) Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson’s disease. N Engl J Med 327: 1549–1555

    Article  PubMed  CAS  Google Scholar 

  7. Friden PM, Walus LR, Musso GF, Taylor MA, Malfroy B, Starzyk R (1991) Antitransferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier. Proc Natl Acad Sci USA 88: 4771–4775

    Article  PubMed  CAS  Google Scholar 

  8. Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde YA (1989) Molecular cloning and expression of brain-derived neurotrophic factor. Nature 341: 149–152

    Article  PubMed  CAS  Google Scholar 

  9. Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237: 1154–1162

    Article  PubMed  CAS  Google Scholar 

  10. Lindvall O, Rehncrona S, Brundin P, Gustavii B, Astedt B, Widner H, Lindholm T, Björklund A, Leenders KL, Rothwell JC, Frackowiak R, Marsden CD, Johnels B, Steg G, Freedman R, Hoffer BJ, Seiger A, Bygdeman M, Strömberg I, Olson L (1989) Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease: A detailed account of methodology and a 6-month follow-up. Arch Neurol 46: 615–631

    Article  PubMed  CAS  Google Scholar 

  11. Backlund E-O, Granberg PO, Hamberger B, Knutsson E, Märtensson A, Sedvall G, Seiger A, Olson L (1985) Transplantation of adrenal medullary tissue to striatum in Parkinsonism. First clinical trials. J Neurosurg 62: 169–173

    Article  PubMed  CAS  Google Scholar 

  12. Olson L (1988) Grafting in the mammalian central nervous system: Basic science with clinical promise. In: Magistretti P (ed) Discussions in neurosciences. FESN, Geneva, pp 1–73

    Google Scholar 

  13. Olson L, Backlund E-O, Ebendal T, Freedman R, Hamberger B, Hansson P, Hoffer B, Lindblom U, Meyerson B, Strömberg I, Sydow O, Seiger A (1991) Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson’s disease: One-year follow-up of first clinical trial. Arch Neurol 48: 373–381

    Article  PubMed  CAS  Google Scholar 

  14. Olson L, Nordberg A, von Holst H, Bäckman L, Ebendal T, Alafuzoff I, Amberla K, Hartvig P, Herlitz A, Lilja A, Lundqvist H, Längström B, Meyerson B, Persson A, Viitanen M, Winblad B, Seiger A (1992) Nerve growth factor affects “C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report). J Neural Transm (Park Dis Dement Sect) 4: 79–95

    Article  CAS  Google Scholar 

  15. Rosenberg MB, Friedmann T, Robertson RC, Tuszynski M, Wolff JA, Breakefield XO, Gage FH (1988) Grafting genetically modified cells to the damaged brain: Restorative effects of NGF expression. Science 242: 1575–1578

    Article  PubMed  CAS  Google Scholar 

  16. Spencer, DD, Robbins RJ, Naftolin F, Marek KL, Vollmer T, Leranth C, Roth RH, Price LH, Gjedde A, Bunney BS, Sass KJ, Elsworth JD, Kier EL, Makuch R, Hoffer PB, Redmond Jr DE (1992) Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson’s disease. N Engl J Med 327: 1541–1548

    Article  PubMed  CAS  Google Scholar 

  17. Strömberg I, Wetmore CJ, Ebendal T, Ernfors P, Persson H, Olson L (1990) Rescue of basal forebrain cholinergic neurons after implantation of genetically modified cells producing recombinant NGF. J Neurosci Res 25: 405–411

    Article  PubMed  Google Scholar 

  18. Thoenen H (1991) The changing scene of neurotrophic factors. Trends Neurosci 14: 165–170

    Article  PubMed  CAS  Google Scholar 

  19. Wetmore C (1992) Brain-derived neurotrophic factor: Studies on the cellular localization and regulation of BDNF, related neurotrophins and their receptors at the mRNA and protein level. Ph.D. Thesis. Karolinska Institutet, Stockholm

    Google Scholar 

  20. Wetmore C, Cao Y, Pettersson RF, Olson L (1991) Brain-derived neurotrophic factor: Subcellular compartmentalization and interneuronal transfer as visualized with antipeptide antibodies. Proc Natl Acad Sci USA 88: 9843–9847

    Article  PubMed  CAS  Google Scholar 

  21. Wetmore C, Bean AJ, Olson L (1992) Regulation of cortical BDNF expression by non-NMDA glutamate receptors (manuscript )

    Google Scholar 

  22. Wetmore C, Cao Y, Pettersson RF, Olson L (1993) Brain-derived neurotrophic factor ( BDNF) peptide antibodies: Characterization using a vaccinia virus expression system. J Histochem Cytochem 41: 521–534

    Article  PubMed  CAS  Google Scholar 

  23. Widner H, Tetrud J, Rehncrona St, Snow B, Brundin P, Gustavii B, Björklund A, Lindvall O, Langston JW. Bilateral foetal mesencephalic grafting in two patients with Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). N Engl J Med 327: 1556–1563

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer-Verlag Wien

About this paper

Cite this paper

Olson, L. (1993). Reparative Strategies in the Brain: Treatment Strategies Based on Trophic Factors and Cell Transfer Techniques. In: Meyerson, B.A., Broggi, G., Martin-Rodriguez, J., Ostertag, C., Sindou, M. (eds) Advances in Stereotactic and Functional Neurosurgery 10. Acta Neurochirurgica, vol 58. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9297-9_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-9297-9_1

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-9299-3

  • Online ISBN: 978-3-7091-9297-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics