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Growth Factor Induction and Order of Events in CNS Repair

  • Chapter
Pharmacological Approaches to the Treatment of Brain and Spinal Cord Injury

Abstract

In response to damage, the adult CNS exhibits capabilities, such as glial cell proliferation and differentiation and axonal sprouting and growth, typical of the developmental period. This “rejuvenation” of the CNS tissue arises as a consequence of the injury-induced increase in the activities of neurotrophic and sprouting factors and of glia, fibroblast, and endothelial cell mitogens and morphogens.

In the absence of neuronal division, true regeneration of the CNS is not possible. However, the knowledge of the biochemical events underlying the cellular response of the CNS to injury offers a way to intervene in the process and attempt functional repair.

Studies on the time course of induction of various growth activities after a lesion reveal that, contrary to what is observed during development, the process of injury repair does not follow a well-ordered temporal sequence. The increase in neurotrophic activity occurs simultaneously with that of axon-sprouting factors and at a time subsequent to most secondary neuronal death. The enhancement in the activity of nonneuronal mitognes (and the consequent proliferation of glial, fibroblast, and endothelial cells) precedes that of axon-sprouting factors. By giving priority to cell proliferation, the organism ensures the restitution of blood supply as well as that of the glia limitans and other CNS-body boundaries. But it compromises the regeneration of axons across the injury area.

This information, accumulated for the most part during the last 5 years, allows us to visualize various ways of intervention after CNS injury. One of the most obvious would be to supply purified neurotrophic factors to the affected area and thus save many neurons from secondary death. Another type of intervention that many of us have in mind is the replacement of lost neurons and their connections by means of transplants. Transplantation of donors CNS tissue at a time when production of neurotrophic and sprouting factors by the injured host is maximal would ensure optimal survival and integration of the donor neurons. Finally, the exogenous supply of purified neurite-sprouting and elongation factors, together wiht that of glial mitogen inhibitors (naturally present in the CNS), may facilitate the regeneration of interrupted pathways.

The purification and use of central growth factors and their inhibitors should eventually permit convergent multiple interventions to repair damaged CNS tissue. Correct timing and intertwining of the requirements of repair with the priorities of the organism seem esential.

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Authors and Affiliations

  1. Department of Psychology, University of California at Irvine, 92717, Irvine, California, USA

    Manuel Nieto-Sampedro

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  1. Manuel Nieto-Sampedro
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Editors and Affiliations

  1. Clark University, Massachusetts, Worcester, USA

    Donald G. Stein

  2. University of Munich, Munich, Federal Republic of Germany

    Bernhard A. Sabel

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© 1988 Plenum Press

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Nieto-Sampedro, M. (1988). Growth Factor Induction and Order of Events in CNS Repair. In: Stein, D.G., Sabel, B.A. (eds) Pharmacological Approaches to the Treatment of Brain and Spinal Cord Injury. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0927-7_15

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  • DOI: https://doi.org/10.1007/978-1-4613-0927-7_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8249-5

  • Online ISBN: 978-1-4613-0927-7

  • eBook Packages: Springer Book Archive

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