Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Apr;84(8):2528–2531. doi: 10.1073/pnas.84.8.2528

Environmental changes induced by growth-associated triggering factors in injured optic nerve of adult rabbit.

Y Bawnik, A Harel, C Stein-Izsak, M Schwartz
PMCID: PMC304687  PMID: 3470808

Abstract

Central nervous system (CNS) neurons of mammals regenerate poorly after axonal injury. However, if an injured CNS neuron (rabbit optic nerve) is supplied with appropriate soluble substances ("growth-associated triggering factors") derived from medium conditioned by regenerating fish optic nerve or newborn rabbit optic nerve, it can express regeneration-associated characteristics. Such characteristics include a general increase in protein synthesis, changes in synthesis of specific polypeptides, and sprouting of nerve fibers in culture. The present study of rabbit optic nerves demonstrates that such active substances affect the neuronal environment (i.e., the non-neuronal cells), thereby perhaps causing a shift in the environment from an inhibitory to a regenerative supportive one. Apparently, such an environment is spontaneously achieved in injured CNS nerves of lower vertebrates (e.g., fish optic nerves), which are regenerable. Treatment of injured rabbit optic nerve with soluble factors from medium conditioned by regenerating carp optic nerve resulted in a selective increase in proliferation ([3H]thymidine incorporation) of perineural cells and the appearance of a 12-kDa polypeptide in a homogenate derived from the nerve and its associated cells. This polypeptide may be related to growth, since it comigrates in NaDodSO4/polyacrylamide gel electrophoresis with a 12-kDa polypeptide that is continuously present in a regenerative system. In addition, there were injury-induced changes in the polypeptides of the nerve that were independent of treatment with conditioned medium and were correlated with nerve maturation. The most prominent changes of this type were in 18-kDa and 25-kDa polypeptides whose levels were reduced after injury and were found to be correlated with the nerve maturation (myelination) state.

Full text

PDF
2528

Images in this article

2529Image
on p.2529
2530Image
on p.2530
2530Image
on p.2530
2530Image
on p.2530

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  2. Hadani M., Harel A., Solomon A., Belkin M., Lavie V., Schwartz M. Substances originating from the optic nerve of neonatal rabbit induce regeneration-associated response in the injured optic nerve of adult rabbit. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7965–7969. doi: 10.1073/pnas.81.24.7965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ignatius M. J., Gebicke-Härter P. J., Skene J. H., Schilling J. W., Weisgraber K. H., Mahley R. W., Shooter E. M. Expression of apolipoprotein E during nerve degeneration and regeneration. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1125–1129. doi: 10.1073/pnas.83.4.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Kato T., Fukui Y., Turriff D. E., Nakagawa S., Lim R., Arnason B. G., Tanaka R. Glia maturation factor in bovine brain: partial purification and physicochemical characterization. Brain Res. 1981 May 18;212(2):393–402. doi: 10.1016/0006-8993(81)90471-6. [DOI] [PubMed] [Google Scholar]
  5. Madison R., da Silva C. F., Dikkes P., Chiu T. H., Sidman R. L. Increased rate of peripheral nerve regeneration using bioresorbable nerve guides and a laminin-containing gel. Exp Neurol. 1985 Jun;88(3):767–772. doi: 10.1016/0014-4886(85)90087-1. [DOI] [PubMed] [Google Scholar]
  6. Molander H., Olsson Y., Engkvist O., Bowald S., Eriksson I. Regeneration of peripheral nerve through a polyglactin tube. Muscle Nerve. 1982 Jan;5(1):54–57. doi: 10.1002/mus.880050110. [DOI] [PubMed] [Google Scholar]
  7. Nieto-Sampedro M., Lewis E. R., Cotman C. W., Manthorpe M., Skaper S. D., Barbin G., Longo F. M., Varon S. Brain injury causes a time-dependent increase in neuronotrophic activity at the lesion site. Science. 1982 Aug 27;217(4562):860–861. doi: 10.1126/science.7100931. [DOI] [PubMed] [Google Scholar]
  8. Nieto-Sampedro M., Manthrope M., Barbin G., Varon S., Cotman C. W. Injury-induced neuronotrophic activity in adult rat brain: correlation with survival of delayed implants in the wound cavity. J Neurosci. 1983 Nov;3(11):2219–2229. doi: 10.1523/JNEUROSCI.03-11-02219.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Nieto-Sampedro M., Whittemore S. R., Needels D. L., Larson J., Cotman C. W. The survival of brain transplants is enhanced by extracts from injured brain. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6250–6254. doi: 10.1073/pnas.81.19.6250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Pellegrino R. G., Spencer P. S. Schwann cell mitosis in response to regenerating peripheral axons in vivo. Brain Res. 1985 Aug 19;341(1):16–25. doi: 10.1016/0006-8993(85)91467-2. [DOI] [PubMed] [Google Scholar]
  11. Quitschke W., Schechter N. 58,000 dalton intermediate filament proteins of neuronal and nonneuronal origin in the goldfish visual pathway. J Neurochem. 1984 Feb;42(2):569–576. doi: 10.1111/j.1471-4159.1984.tb02715.x. [DOI] [PubMed] [Google Scholar]
  12. Rachailovich I., Schwartz M. Molecular events associated with increased regenerative capacity of the goldfish retinal ganglion cells following X-irradiation: decreased level of axonal growth inhibitors. Brain Res. 1984 Jul 23;306(1-2):149–155. doi: 10.1016/0006-8993(84)90363-9. [DOI] [PubMed] [Google Scholar]
  13. Richardson P. M., McGuinness U. M., Aguayo A. J. Axons from CNS neurons regenerate into PNS grafts. Nature. 1980 Mar 20;284(5753):264–265. doi: 10.1038/284264a0. [DOI] [PubMed] [Google Scholar]
  14. Schwartz M., Belkin M., Harel A., Solomon A., Lavie V., Hadani M., Rachailovich I., Stein-Izsak C. Regenerating fish optic nerves and a regeneration-like response in injured optic nerves of adult rabbits. Science. 1985 May 3;228(4699):600–603. doi: 10.1126/science.3983646. [DOI] [PubMed] [Google Scholar]
  15. Skene J. H., Shooter E. M. Denervated sheath cells secrete a new protein after nerve injury. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4169–4173. doi: 10.1073/pnas.80.13.4169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Snipes G. J., McGuire C. B., Norden J. J., Freeman J. A. Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1130–1134. doi: 10.1073/pnas.83.4.1130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Solomon A., Belkin M., Hadani M., Harel A., Rachailovich I., Lavie V., Schwartz M. A new transorbital surgical approach to the rabbit's optic nerve. J Neurosci Methods. 1985 Jan;12(3):259–262. doi: 10.1016/0165-0270(85)90009-3. [DOI] [PubMed] [Google Scholar]
  18. Williams L. R., Varon S. Modification of fibrin matrix formation in situ enhances nerve regeneration in silicone chambers. J Comp Neurol. 1985 Jan 8;231(2):209–220. doi: 10.1002/cne.902310208. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES