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. 1997 Jan;190(Pt 1):5–21. doi: 10.1046/j.1469-7580.1997.19010005.x

Glial–glial and glial–neuronal interfaces in radiation-induced, glia-depleted spinal cord

SHIRLEY ANN GILMORE ✉, TERRY J SIMS 1
PMCID: PMC1467580  PMID: 9034878

Abstract

This review summarises some of the major findings derived from studies using the model of a glia-depleted environment developed and characterised in this laboratory. Glial depletion is achieved by exposure of the immature rodent spinal cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte populations and severely impairs myelination. This glia-depleted, hypomyelinated state presents a unique opportunity to examine aspects of spinal cord maturation in the absence of a normal glial population. An associated sequela within 2–3 wk following irradiation is the appearance of Schwann cells in the dorsal portion of the spinal cord. Characteristics of these intraspinal Schwann cells, their patterns of myelination or ensheathment, and their interrelations with the few remaining central glia have been examined. A later sequela is the development of Schwann cells in the ventral aspect of the spinal cord where they occur predominantly in the grey matter. Characteristics of these ventrally situated intraspinal Schwann cells are compared with those of Schwann cells located dorsally. Recently, injury responses have been defined in the glia-depleted spinal cord subsequent to the lesioning of dorsal spinal nerve roots. In otherwise normal animals, dorsal nerve root injury induces an astrocytic reaction within the spinal segments with which the root(s) is/are associated. Lesioning of the 4th lumbar dorsal root on the right side in irradiated or nonirradiated animals results in markedly different glial responses with little astrocytic scarring in the irradiated animals. Tracing studies reveal that these lesioned dorsal root axons regrow rather robustly into the spinal cord in irradiated but not in nonirradiated animals. To examine role(s) of glial cells in preventing this axonal regrowth, glial cells are now being added back to this glia-depleted environment through transplantation of cultured glia into the irradiated area. Transplanted astrocytes establish barrier-like arrangements within the irradiated cords and prevent axonal regrowth into the cord. Studies using other types of glial cultures (oligodendrocyte or mixed) are ongoing.

Keywords: Astrocytes, oligodendrocytes, myelin, Schwann cells, x-irradiation

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Selected References

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  1. Beal J. A., Hall J. L. A light microscopic study of the effects of X-irradiation on the spinal cord of neonatal rats. J Neuropathol Exp Neurol. 1974 Jan;33(1):128–143. doi: 10.1097/00005072-197401000-00010. [DOI] [PubMed] [Google Scholar]
  2. Black J. A., Sims T. J., Waxman S. G., Gilmore S. A. Membrane ultrastructure of developing axons in glial cell deficient rat spinal cord. J Neurocytol. 1985 Feb;14(1):79–104. doi: 10.1007/BF01150264. [DOI] [PubMed] [Google Scholar]
  3. Black J. A., Waxman S. G. The perinodal astrocyte. Glia. 1988;1(3):169–183. doi: 10.1002/glia.440010302. [DOI] [PubMed] [Google Scholar]
  4. Blakemore W. F. Limited remyelination of CNS axons by Schwann cells transplanted into the sub-arachnoid space. J Neurol Sci. 1984 Jun;64(3):265–276. doi: 10.1016/0022-510x(84)90175-8. [DOI] [PubMed] [Google Scholar]
  5. Blakemore W. F. Remyelination of CNS axons by Schwann cells transplanted from the sciatic nerve. Nature. 1977 Mar 3;266(5597):68–69. doi: 10.1038/266068a0. [DOI] [PubMed] [Google Scholar]
  6. Brook G. A., Lawrence J. M., Raisman G. Morphology and migration of cultured Schwann cells transplanted into the fimbria and hippocampus in adult rats. Glia. 1993 Dec;9(4):292–304. doi: 10.1002/glia.440090407. [DOI] [PubMed] [Google Scholar]
  7. Cadelli D. S., Bandtlow C. E., Schwab M. E. Oligodendrocyte- and myelin-associated inhibitors of neurite outgrowth: their involvement in the lack of CNS regeneration. Exp Neurol. 1992 Jan;115(1):189–192. doi: 10.1016/0014-4886(92)90246-m. [DOI] [PubMed] [Google Scholar]
  8. Dal Canto M. C., Barbano R. L. Remyelination during remission in Theiler's virus infection. Am J Pathol. 1984 Jul;116(1):30–45. [PMC free article] [PubMed] [Google Scholar]
  9. Duncan I. D., Hammang J. P., Gilmore S. A. Schwann cell myelination of the myelin deficient rat spinal cord following X-irradiation. Glia. 1988;1(3):233–239. doi: 10.1002/glia.440010309. [DOI] [PubMed] [Google Scholar]
  10. Franklin R. J., Blakemore W. F. Requirements for Schwann cell migration within CNS environments: a viewpoint. Int J Dev Neurosci. 1993 Oct;11(5):641–649. doi: 10.1016/0736-5748(93)90052-F. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. GILMORE S. A. The effects of x-irradiation on the spinal cords of neonatal rats. II. Histological observations. J Neuropathol Exp Neurol. 1963 Apr;22:294–301. doi: 10.1097/00005072-196304000-00008. [DOI] [PubMed] [Google Scholar]
  12. Gilmore S. A. Autoradiographic studies of intramedullary Schwann cells in irradiated spinal cords of immature rats. Anat Rec. 1971 Dec;171(4):517–528. doi: 10.1002/ar.1091710408. [DOI] [PubMed] [Google Scholar]
  13. Gilmore S. A., Duncan D. On the presence of peripheral-like nervous and connective tissue within irradiated spinal cord. Anat Rec. 1968 Apr;160(4):675–690. doi: 10.1002/ar.1091600403. [DOI] [PubMed] [Google Scholar]
  14. Gilmore S. A. Neuroglial population in the spinal white matter of neonatal and early postnatal rats: an autoradiographic study of numbers of neuroglia and changes in their proliferative activity. Anat Rec. 1971 Oct;171(2):283–291. doi: 10.1002/ar.1091710208. [DOI] [PubMed] [Google Scholar]
  15. Gilmore S. A., Phillips N., White P., Sims T. J. Schwann cell induction in the ventral portion of the spinal cord. Brain Res Bull. 1993;30(3-4):339–345. doi: 10.1016/0361-9230(93)90262-a. [DOI] [PubMed] [Google Scholar]
  16. Gilmore S. A., Sims T. J., Heard J. K. Autoradiographic and ultrastructural studies of areas of spinal cord occupied by Schwann cells and Schwann cell myelin. Brain Res. 1982 May 13;239(2):365–375. doi: 10.1016/0006-8993(82)90515-7. [DOI] [PubMed] [Google Scholar]
  17. Harrison B. Schwann cell and oligodendrocyte remyelination in lysolecithin-induced lesions in irradiated rat spinal cord. J Neurol Sci. 1985 Feb;67(2):143–159. doi: 10.1016/0022-510x(85)90111-x. [DOI] [PubMed] [Google Scholar]
  18. Heard J. K., Gilmore S. A. A comparison of histopathologic changes following X-irradiation of mid-thoracic and lumbosacral levels of neonatal rat spinal cord. Anat Rec. 1985 Feb;211(2):198–204. doi: 10.1002/ar.1092110212. [DOI] [PubMed] [Google Scholar]
  19. Heard J. K., Gilmore S. A. Intramedullary Schwann cell development following x-irradiation of mid-thoracic and lumbosacral spinal cord levels in immature rats. Anat Rec. 1980 May;197(1):85–93. doi: 10.1002/ar.1091970108. [DOI] [PubMed] [Google Scholar]
  20. Hildebrand C. Ultrastructural and light-microscopic studies of the nodal region in large myelinated fibres of the adult feline spinal cord white matter. Acta Physiol Scand Suppl. 1971;364:43–79. doi: 10.1111/j.1365-201x.1971.tb10978.x. [DOI] [PubMed] [Google Scholar]
  21. Liuzzi F. J., Lasek R. J. Astrocytes block axonal regeneration in mammals by activating the physiological stop pathway. Science. 1987 Aug 7;237(4815):642–645. doi: 10.1126/science.3603044. [DOI] [PubMed] [Google Scholar]
  22. Liuzzi F. J. Proteolysis is a critical step in the physiological stop pathway: mechanisms involved in the blockade of axonal regeneration by mammalian astrocytes. Brain Res. 1990 Apr 2;512(2):277–283. doi: 10.1016/0006-8993(90)90637-Q. [DOI] [PubMed] [Google Scholar]
  23. Molander C., Grant G. Laminar distribution and somatotopic organization of primary afferent fibers from hindlimb nerves in the dorsal horn. A study by transganglionic transport of horseradish peroxidase in the rat. Neuroscience. 1986 Sep;19(1):297–312. doi: 10.1016/0306-4522(86)90023-0. [DOI] [PubMed] [Google Scholar]
  24. Murray M., Wang S. D., Goldberger M. E., Levitt P. Modification of astrocytes in the spinal cord following dorsal root or peripheral nerve lesions. Exp Neurol. 1990 Dec;110(3):248–257. doi: 10.1016/0014-4886(90)90036-r. [DOI] [PubMed] [Google Scholar]
  25. Nathaniel E. J., Nathaniel D. R. Astroglial response to degeneration of dorsal root fibers in adult rat spinal cord. Exp Neurol. 1977 Jan;54(1):60–76. doi: 10.1016/0014-4886(77)90235-7. [DOI] [PubMed] [Google Scholar]
  26. Nathaniel E. J., Nathaniel D. R. Degeneration of dorsal roots in the adult rat spinal cord. Exp Neurol. 1973 Aug;40(2):316–332. doi: 10.1016/0014-4886(73)90077-0. [DOI] [PubMed] [Google Scholar]
  27. Raine C. S., Traugott U., Stone S. H. Glial bridges and Schwann cell migration during chronic demyelination in the C.N.S. J Neurocytol. 1978 Oct;7(5):541–553. doi: 10.1007/BF01260888. [DOI] [PubMed] [Google Scholar]
  28. Raisman G., Lawrence J. M., Brook G. A. Schwann cells transplanted into the CNS. Int J Dev Neurosci. 1993 Oct;11(5):651–669. doi: 10.1016/0736-5748(93)90053-g. [DOI] [PubMed] [Google Scholar]
  29. Reier P. J., Houle J. D. The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair. Adv Neurol. 1988;47:87–138. [PubMed] [Google Scholar]
  30. Rivero-Melián C., Grant G. Distribution of lumbar dorsal root fibers in the lower thoracic and lumbosacral spinal cord of the rat studied with choleragenoid horseradish peroxidase conjugate. J Comp Neurol. 1990 Sep 22;299(4):470–481. doi: 10.1002/cne.902990407. [DOI] [PubMed] [Google Scholar]
  31. Rudge J. S., Silver J. Inhibition of neurite outgrowth on astroglial scars in vitro. J Neurosci. 1990 Nov;10(11):3594–3603. doi: 10.1523/JNEUROSCI.10-11-03594.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sasaki M., Ide C. Demyelination and remyelination in the dorsal funiculus of the rat spinal cord after heat injury. J Neurocytol. 1989 Apr;18(2):225–239. doi: 10.1007/BF01206664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schnell L., Schwab M. E. Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature. 1990 Jan 18;343(6255):269–272. doi: 10.1038/343269a0. [DOI] [PubMed] [Google Scholar]
  34. Schwab M. E., Caroni P. Oligodendrocytes and CNS myelin are nonpermissive substrates for neurite growth and fibroblast spreading in vitro. J Neurosci. 1988 Jul;8(7):2381–2393. doi: 10.1523/JNEUROSCI.08-07-02381.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sims T. J., Gilmore S. A. Glial response to dorsal root lesion in the irradiated spinal cord. Glia. 1992;6(2):96–107. doi: 10.1002/glia.440060204. [DOI] [PubMed] [Google Scholar]
  36. Sims T. J., Gilmore S. A. Interactions between Schwann cells and CNS axons following a delay in the normal formation of central myelin. Exp Brain Res. 1989;75(3):513–522. doi: 10.1007/BF00249902. [DOI] [PubMed] [Google Scholar]
  37. Sims T. J., Gilmore S. A. Interactions between intraspinal Schwann cells and the cellular constituents normally occurring in the spinal cord: an ultrastructural study in the irradiated rat. Brain Res. 1983 Oct 3;276(1):17–30. doi: 10.1016/0006-8993(83)90544-9. [DOI] [PubMed] [Google Scholar]
  38. Sims T. J., Gilmore S. A. Regeneration of dorsal root axons into experimentally altered glial environments in the rat spinal cord. Exp Brain Res. 1994;99(1):25–33. doi: 10.1007/BF00241409. [DOI] [PubMed] [Google Scholar]
  39. Sims T. J., Gilmore S. A. Regrowth of dorsal root axons into a radiation-induced glial-deficient environment in the spinal cord. Brain Res. 1994 Jan 14;634(1):113–126. doi: 10.1016/0006-8993(94)90264-x. [DOI] [PubMed] [Google Scholar]
  40. Sims T. J., Gilmore S. A., Waxman S. G., Klinge E. Dorsal-ventral differences in the glia limitans of the spinal cord: an ultrastructural study in developing normal and irradiated rats. J Neuropathol Exp Neurol. 1985 Jul;44(4):415–429. doi: 10.1097/00005072-198507000-00005. [DOI] [PubMed] [Google Scholar]
  41. Sims T. J., Waxman S. G., Black J. A., Gilmore S. A. Perinodal astrocytic processes at nodes of Ranvier in developing normal and glial cell deficient rat spinal cord. Brain Res. 1985 Jul 1;337(2):321–331. doi: 10.1016/0006-8993(85)90069-1. [DOI] [PubMed] [Google Scholar]

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