Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The bright side of the glial scar in CNS repair

Abstract

Following CNS injury, in an apparently counterintuitive response, scar tissue formation inhibits axonal growth, imposing a major barrier to regeneration. Accordingly, scar-modulating treatments have become a leading therapeutic goal in the field of spinal cord injury. However, increasing evidence suggests a beneficial role for this scar tissue as part of the endogenous local immune regulation and repair process. How can these opposing effects be reconciled? Perhaps it is all a matter of timing.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Scar components and potential therapeutic interventions.
Figure 2: The repair process as a function of time and the effects of the scar.

References

  1. Nesathurai, S. Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials. J. Trauma 45, 1088–1093 (1998).

    CAS  PubMed  Google Scholar 

  2. Caroni, P. & Schwab, M. E. Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1, 85–96 (1988).

    CAS  PubMed  Google Scholar 

  3. McKerracher, L. et al. Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 13, 805–811 (1994).

    CAS  PubMed  Google Scholar 

  4. Mukhopadhyay, G., Doherty, P., Walsh, F. S., Crocker, P. R. & Filbin, M. T. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13, 757–767 (1994).

    CAS  PubMed  Google Scholar 

  5. Jones, L. L., Margolis, R. U. & Tuszynski, M. H. The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp. Neurol. 182, 399–411 (2003).

    CAS  PubMed  Google Scholar 

  6. Gallo, V., Bertolotto, A. & Levi, G. The proteoglycan chondroitin sulfate is present in a subpopulation of cultured astrocytes and in their precursors. Dev. Biol. 123, 282–285 (1987).

    CAS  PubMed  Google Scholar 

  7. Katoh-Semba, R., Matsuda, M., Kato, K. & Oohira, A. Chondroitin sulphate proteoglycans in the rat brain: candidates for axon barriers of sensory neurons and the possible modification by laminin of their actions. Eur. J. Neurosci. 7, 613–621 (1995).

    CAS  PubMed  Google Scholar 

  8. Tang, X., Davies, J. E. & Davies, S. J. Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue. J. Neurosci. Res. 71, 427–444 (2003).

    CAS  PubMed  Google Scholar 

  9. McKeon, R. J., Jurynec, M. J. & Buck, C. R. The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. J. Neurosci. 19, 10778–10788 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Tester, N. J. & Howland, D. R. Chondroitinase ABC improves basic and skilled locomotion in spinal cord injured cats. Exp. Neurol. 209, 483–496 (2008).

    CAS  PubMed  Google Scholar 

  11. Moon, L. D., Asher, R. A., Rhodes, K. E. & Fawcett, J. W. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nature Neurosci. 4, 465–466 (2001).

    CAS  PubMed  Google Scholar 

  12. Bradbury, E. J. et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416, 636–640 (2002).

    CAS  PubMed  Google Scholar 

  13. Caggiano, A. O., Zimber, M. P., Ganguly, A., Blight, A. R. & Gruskin, E. A. Chondroitinase ABCI improves locomotion and bladder function following contusion injury of the rat spinal cord. J. Neurotrauma 22, 226–239 (2005).

    PubMed  Google Scholar 

  14. Tan, A. M., Colletti, M., Rorai, A. T., Skene, J. H. & Levine, J. M. Antibodies against the NG2 proteoglycan promote the regeneration of sensory axons within the dorsal columns of the spinal cord. J. Neurosci. 26, 4729–4739 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Neumann, S., Bradke, F., Tessier-Lavigne, M. & Basbaum, A. I. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 34, 885–893 (2002).

    CAS  PubMed  Google Scholar 

  16. Borisoff, J. F. et al. Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates. Mol. Cell. Neurosci. 22, 405–416 (2003).

    CAS  PubMed  Google Scholar 

  17. Dergham, P. et al. Rho signaling pathway targeted to promote spinal cord repair. J. Neurosci. 22, 6570–6577 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Monnier, P. P., Sierra, A., Schwab, J. M., Henke-Fahle, S. & Mueller, B. K. The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Mol. Cell. Neurosci. 22, 319–330 (2003).

    CAS  PubMed  Google Scholar 

  19. Tian, D. S. et al. Attenuation of astrogliosis by suppressing of microglial proliferation with the cell cycle inhibitor olomoucine in rat spinal cord injury model. Brain Res. 1154, 206–214 (2007).

    CAS  PubMed  Google Scholar 

  20. Zhang, Y., Dijkhuizen, P. A., Anderson, P. N., Lieberman, A. R. & Verhaagen, J. NT-3 delivered by an adenoviral vector induces injured dorsal root axons to regenerate into the spinal cord of adult rats. J. Neurosci. Res. 54, 554–562 (1998).

    CAS  PubMed  Google Scholar 

  21. Romero, M. I., Rangappa, N., Garry, M. G. & Smith, G. M. Functional regeneration of chronically injured sensory afferents into adult spinal cord after neurotrophin gene therapy. J. Neurosci. 21, 8408–8416 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Grimpe, B. & Silver, J. A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord. J. Neurosci. 24, 1393–1397 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Silver, J. & Miller, J. H. Regeneration beyond the glial scar. Nature Rev. Neurosci. 5, 146–156 (2004).

    CAS  Google Scholar 

  24. Fawcett, J. W. Overcoming inhibition in the damaged spinal cord. J. Neurotrauma 23, 371–383 (2006).

    PubMed  Google Scholar 

  25. Yiu, G. & He, Z. Glial inhibition of CNS axon regeneration. Nature Rev. Neurosci. 7, 617–627 (2006).

    CAS  Google Scholar 

  26. McKeon, R. J., Schreiber, R. C., Rudge, J. S. & Silver, J. Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J. Neurosci. 11, 3398–3411 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Smith-Thomas, L. C. et al. An inhibitor of neurite outgrowth produced by astrocytes. J. Cell Sci. 107, 1687–1695 (1994).

    CAS  PubMed  Google Scholar 

  28. Fidler, P. S. et al. Comparing astrocytic cell lines that are inhibitory or permissive for axon growth: the major axon-inhibitory proteoglycan is NG2. J. Neurosci. 19, 8778–8788 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Snow, D. M., Steindler, D. A. & Silver, J. Molecular and cellular characterization of the glial roof plate of the spinal cord and optic tectum: a possible role for a proteoglycan in the development of an axon barrier. Dev. Biol. 138, 359–376 (1990).

    CAS  PubMed  Google Scholar 

  30. Faissner, A. et al. Isolation of a neural chondroitin sulfate proteoglycan with neurite outgrowth promoting properties. J. Cell Biol. 126, 783–799 (1994).

    CAS  PubMed  Google Scholar 

  31. Smith-Thomas, L. C. et al. Increased axon regeneration in astrocytes grown in the presence of proteoglycan synthesis inhibitors. J. Cell Sci. 108, 1307–1315 (1995).

    CAS  PubMed  Google Scholar 

  32. Tom, V. J. & Houle, J. D. Intraspinal microinjection of chondroitinase ABC following injury promotes axonal regeneration out of a peripheral nerve graft bridge. Exp. Neurol. 211, 315–319 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Hikino, M. et al. Oversulfated dermatan sulfate exhibits neurite outgrowth-promoting activity toward embryonic mouse hippocampal neurons: implications of dermatan sulfate in neuritogenesis in the brain. J. Biol. Chem. 278, 43744–43754 (2003).

    CAS  PubMed  Google Scholar 

  34. Bicknese, A. R., Sheppard, A. M., O'Leary, D. D. & Pearlman, A. L. Thalamocortical axons extend along a chondroitin sulfate proteoglycan-enriched pathway coincident with the neocortical subplate and distinct from the efferent path. J. Neurosci. 14, 3500–3510 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Sato, Y. et al. A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death. J. Neurochem. 104, 1565–1576 (2008).

    CAS  PubMed  Google Scholar 

  36. Nakanishi, K. et al. Identification of neurite outgrowth-promoting domains of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, and involvement of phosphatidylinositol 3-kinase and protein kinase C signaling pathways in neuritogenesis. J. Biol. Chem. 281, 24970–24978 (2006).

    CAS  PubMed  Google Scholar 

  37. Brittis, P. A. & Silver, J. Exogenous glycosaminoglycans induce complete inversion of retinal ganglion cell bodies and their axons within the retinal neuroepithelium. Proc. Natl Acad. Sci. USA 91, 7539–7542 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Greenfield, B. et al. Characterization of the heparan sulfate and chondroitin sulfate assembly sites in CD44. J. Biol. Chem. 274, 2511–2517 (1999).

    CAS  PubMed  Google Scholar 

  39. Nichol, K. A., Everett, A. W., Schulz, M. & Bennett, M. R. Retinal ganglion cell survival in vitro maintained by a chondroitin sulfate proteoglycan from the superior colliculus carrying the HNK-1 epitope. J. Neurosci. Res. 37, 623–632 (1994).

    CAS  PubMed  Google Scholar 

  40. Fitch, M. T. & Silver, J. Activated macrophages and the blood-brain barrier: inflammation after CNS injury leads to increases in putative inhibitory molecules. Exp. Neurol. 148, 587–603 (1997).

    CAS  PubMed  Google Scholar 

  41. Reier, P. J. & Houle, J. D. The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair. Adv. Neurol. 47, 87–138 (1988).

    CAS  PubMed  Google Scholar 

  42. Cui, W., Allen, N. D., Skynner, M., Gusterson, B. & Clark, A. J. Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain. Glia 34, 272–282 (2001).

    CAS  PubMed  Google Scholar 

  43. Chen, Y. et al. Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism. J. Neurochem. 77, 1601–1610 (2001).

    CAS  PubMed  Google Scholar 

  44. Roitbak, T. & Sykova, E. Diffusion barriers evoked in the rat cortex by reactive astrogliosis. Glia 28, 40–48 (1999).

    CAS  PubMed  Google Scholar 

  45. Vorisek, I., Hajek, M., Tintera, J., Nicolay, K. & Sykova, E. Water ADC, extracellular space volume, and tortuosity in the rat cortex after traumatic injury. Magn. Reson. Med. 48, 994–1003 (2002).

    CAS  PubMed  Google Scholar 

  46. do Carmo Cunha, J. et al. Responses of reactive astrocytes containing S100β protein and fibroblast growth factor-2 in the border and in the adjacent preserved tissue after a contusion injury of the spinal cord in rats: implications for wound repair and neuroregeneration. Wound Repair Regen. 15, 134–146 (2007).

    PubMed  Google Scholar 

  47. White, R. E., Yin, F. Q. & Jakeman, L. B. TGF-a increases astrocyte invasion and promotes axonal growth into the lesion following spinal cord injury in mice. Exp. Neurol. 214, 10–24 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Wu, V. W., Nishiyama, N. & Schwartz, J. P. A culture model of reactive astrocytes: increased nerve growth factor synthesis and reexpression of cytokine responsiveness. J. Neurochem. 71, 749–756 (1998).

    CAS  PubMed  Google Scholar 

  49. Schwartz, J. P. & Nishiyama, N. Neurotrophic factor gene expression in astrocytes during development and following injury. Brain Res. Bull. 35, 403–407 (1994).

    CAS  PubMed  Google Scholar 

  50. Stichel, C. C. & Muller, H. W. The CNS lesion scar: new vistas on an old regeneration barrier. Cell Tissue Res. 294, 1–9 (1998).

    CAS  PubMed  Google Scholar 

  51. Parri, R. & Crunelli, V. An astrocyte bridge from synapse to blood flow. Nature Neurosci. 6, 5–6 (2003).

    CAS  PubMed  Google Scholar 

  52. Faulkner, J. R. et al. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J. Neurosci. 24, 2143–2155 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Bush, T. G. et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23, 297–308 (1999).

    CAS  PubMed  Google Scholar 

  54. Schwartz, M., Butovsky, O. & Kipnis, J. Does inflammation in an autoimmune disease differ from inflammation in neurodegenerative diseases? Possible implications for therapy. J. Neuroimmune Pharmacol. 1, 4–10 (2006).

    PubMed  Google Scholar 

  55. Glezer, I., Simard, A. R. & Rivest, S. Neuroprotective role of the innate immune system by microglia. Neuroscience 147, 867–883 (2007).

    CAS  PubMed  Google Scholar 

  56. Garg, S. K., Banerjee, R. & Kipnis, J. Neuroprotective immunity: T cell-derived glutamate endows astrocytes with a neuroprotective phenotype. J. Immunol. 180, 3866–3873 (2008).

    CAS  PubMed  Google Scholar 

  57. Horn, K. P., Busch, S. A., Hawthorne, A. L., van Rooijen, N. & Silver, J. Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. J. Neurosci. 28, 9330–9341 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Popovich, P. G. et al. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp. Neurol. 158, 351–365 (1999).

    CAS  PubMed  Google Scholar 

  59. Prewitt, C. M., Niesman, I. R., Kane, C. J. & Houle, J. D. Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord. Exp. Neurol. 148, 433–443 (1997).

    CAS  PubMed  Google Scholar 

  60. Rapalino, O. et al. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nature Med. 4, 814–821 (1998).

    CAS  PubMed  Google Scholar 

  61. Rhodes, K. E., Moon, L. D. & Fawcett, J. W. Inhibiting cell proliferation during formation of the glial scar: effects on axon regeneration in the CNS. Neuroscience 120, 41–56 (2003).

    CAS  PubMed  Google Scholar 

  62. Myer, D. J., Gurkoff, G. G., Lee, S. M., Hovda, D. A. & Sofroniew, M. V. Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129, 2761–2772 (2006).

    CAS  PubMed  Google Scholar 

  63. Okada, S. et al. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nature Med. 12, 829–834 (2006).

    CAS  PubMed  Google Scholar 

  64. Herrmann, J. E. et al. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J. Neurosci. 28, 7231–7243 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Chung, I. Y. & Benveniste, E. N. Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. J. Immunol. 144, 2999–3007 (1990).

    CAS  PubMed  Google Scholar 

  66. Nandini, C. D. & Sugahara, K. Role of the sulfation pattern of chondroitin sulfate in its biological activities and in the binding of growth factors. Adv. Pharmacol. 53, 253–279 (2006).

    CAS  PubMed  Google Scholar 

  67. Rolls, A. et al. Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med. 5, e171 (2008).

    PubMed  PubMed Central  Google Scholar 

  68. Hayashi, K., Kadomatsu, K. & Muramatsu, T. Requirement of chondroitin sulfate/dermatan sulfate recognition in midkine-dependent migration of macrophages. Glycoconj. J. 18, 401–406 (2001).

    CAS  PubMed  Google Scholar 

  69. Kodaira, Y., Nair, S. K., Wrenshall, L. E., Gilboa, E. & Platt, J. L. Phenotypic and functional maturation of dendritic cells mediated by heparan sulfate. J. Immunol. 165, 1599–1604 (2000).

    CAS  PubMed  Google Scholar 

  70. Rolls, A. et al. A sulfated disaccharide derived from chondroitin sulfate proteoglycan protects against inflammation-associated neurodegeneration. FASEB J. 20, 547–549 (2006).

    CAS  PubMed  Google Scholar 

  71. Laywell, E. D., Steindler, D. A. & Silver, D. J. Astrocytic stem cells in the adult brain. Neurosurg. Clin. N. Am. 18, 21–30 (2007).

    PubMed  Google Scholar 

  72. Walton, N. M. et al. Derivation and large-scale expansion of multipotent astroglial neural progenitors from adult human brain. Development 133, 3671–3681 (2006).

    CAS  PubMed  Google Scholar 

  73. Ma, D. K., Ming, G. L. & Song, H. Glial influences on neural stem cell development: cellular niches for adult neurogenesis. Curr. Opin. Neurobiol. 15, 514–520 (2005).

    CAS  PubMed  Google Scholar 

  74. Ulloa, F. & Briscoe, J. Morphogens and the control of cell proliferation and patterning in the spinal cord. Cell Cycle 6, 2640–2649 (2007).

    CAS  PubMed  Google Scholar 

  75. Gates, M. A. et al. Cell and molecular analysis of the developing and adult mouse subventricular zone of the cerebral hemispheres. J. Comp. Neurol. 361, 249–266 (1995).

    CAS  PubMed  Google Scholar 

  76. Ida, M. et al. Identification and functions of chondroitin sulfate in the milieu of neural stem cells. J. Biol. Chem. 281, 5982–5991 (2006).

    CAS  PubMed  Google Scholar 

  77. Akita, K. et al. Expression of multiple chondroitin/dermatan sulfotransferases in the neurogenic regions of the embryonic and adult central nervous system implies that complex chondroitin sulfates have a role in neural stem cell maintenance. Stem Cells 26, 798–809 (2008).

    CAS  PubMed  Google Scholar 

  78. Garwood, J. et al. The extracellular matrix glycoprotein Tenascin-C is expressed by oligodendrocyte precursor cells and required for the regulation of maturation rate, survival and responsiveness to platelet-derived growth factor. Eur. J. Neurosci. 20, 2524–2540 (2004).

    PubMed  Google Scholar 

  79. Garcion, E., Faissner, A. & ffrench-Constant, C. Knockout mice reveal a contribution of the extracellular matrix molecule tenascin-C to neural precursor proliferation and migration. Development 128, 2485–2496 (2001).

    CAS  PubMed  Google Scholar 

  80. Sirko, S., von Holst, A., Wizenmann, A., Gotz, M. & Faissner, A. Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells. Development 134, 2727–2738 (2007).

    CAS  PubMed  Google Scholar 

  81. Sato, Y. et al. Reduction of brain injury in neonatal hypoxic-ischemic rats by intracerebroventricular injection of neural stem/progenitor cells together with chondroitinase ABC. Reprod. Sci. 15, 613–620 (2008).

    PubMed  Google Scholar 

  82. Rolls, A. et al. Toll-like receptors modulate adult hippocampal neurogenesis. Nature Cell. Biol. 9, 1081–1088 (2007).

    CAS  PubMed  Google Scholar 

  83. Shechter, R. et al. Toll-like receptor 4 restricts retinal progenitor cell proliferation. J. Cell Biol. 183, 393–400 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Ebert, S. et al. Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype. J. Leukoc. Biol. 84, 736–740 (2008).

    CAS  PubMed  Google Scholar 

  85. Rolls, A. et al. A disaccharide derived from chondroitin sulphate proteoglycan promotes central nervous system repair in rats and mice. Eur. J. Neurosci. 20, 1973–1983 (2004).

    PubMed  Google Scholar 

  86. Coumans, J. V. et al. Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins. J. Neurosci. 21, 9334–9344 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Iarikov, D. E. et al. Delayed transplantation with exogenous neurotrophin administration enhances plasticity of corticofugal projections after spinal cord injury. J. Neurotrauma 24, 690–702 (2007).

    PubMed  Google Scholar 

  88. Sofroniew, M. V. Reactive astrocytes in neural repair and protection. Neuroscientist 11, 400–407 (2005).

    CAS  PubMed  Google Scholar 

  89. Rapalino, O. et al. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nature Med. 4, 814–821 (1998).

    CAS  PubMed  Google Scholar 

  90. Moalem, G. et al. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nature Med. 5, 49–55 (1999).

    CAS  PubMed  Google Scholar 

  91. Ziv, Y. et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nature Neurosci. 9, 268–275 (2006).

    CAS  PubMed  Google Scholar 

  92. Ziv, Y., Avidan, H., Pluchino, S., Martino, G. & Schwartz, M. Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury. Proc. Natl Acad. Sci. USA 103, 13174–13179 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Kipnis, J., Derecki, N. C., Yang, C. & Scrable, H. Immunity and cognition: what do age-related dementia, HIV-dementia and 'chemo-brain' have in common? Trends Immunol. 29, 455–463 (2008).

    CAS  PubMed  Google Scholar 

  94. Butovsky, O., Kunis, G., Koronyo-Hamaoui, M. & Schwartz, M. Selective ablation of bone marrow-derived dendritic cells increases amyloid plaques in a mouse Alzheimer's disease model. Eur. J. Neurosci. 26, 413–416 (2007).

    PubMed  Google Scholar 

  95. Simard, A. R., Soulet, D., Gowing, G., Julien, J. P. & Rivest, S. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 49, 489–502 (2006).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank U. Nevo, for his invaluable contribution to concept development when he was a graduate student in this group, and S. Schwarzbaum. The work was supported in part by the High Q foundation and by IsrALS.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michal Schwartz.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rolls, A., Shechter, R. & Schwartz, M. The bright side of the glial scar in CNS repair. Nat Rev Neurosci 10, 235–241 (2009). https://doi.org/10.1038/nrn2591

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2591

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing