Glial scar and immune cell involvement in tissue remodeling and repair following acute CNS injuries

GLIA

Volumn 62, Issue 11, 2014, Pages 1895-1904

  Raposo, Catarina ^a   Schwartz, Michal ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

Acute trauma; Axonal regeneration; Glial scar; Microglia; Monocyte derived macrophages

Indexed keywords

GROWTH FACTOR;

CELL INFILTRATION; CELL SURVIVAL; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM DISEASE; GLIA CELL; HEALING; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOREGULATION; INFLAMMATION; MACROPHAGE; NERVE FIBER; NERVE REGENERATION; NERVE SPROUTING; NERVOUS TISSUE; NEUROLOGIC DISEASE; NEUROPROTECTION; REVIEW; SCAR; ACUTE DISEASE; ANIMAL; CONVALESCENCE; GLIA; IMMUNOLOGY; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY;

ACUTE DISEASE; ANIMALS; CENTRAL NERVOUS SYSTEM DISEASES; CICATRIX; HUMANS; MACROPHAGES; NEUROGLIA; RECOVERY OF FUNCTION;

EID: 84912526221     PISSN: 08941491     EISSN: 10981136     Source Type: Journal    
DOI: 10.1002/glia.22676     Document Type: Review

References (116)

1. Afshari FT, Kappagantula S, Fawcett JW. 2009. Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury. Exp Rev Mol Med 11:e37.
2. Arnold L, Henry A, Poron F, Baba-Amer Y, van Rooijen N, Plonquet A, Gherardi RK, Chazaud B. 2007. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 204:1057-1069.
3. Arwert EN, Hoste E, Watt FM. 2012. Epithelial stem cells, wound healing and cancer. Nat Rev Cancer 12:170-180.
4. Barouch R, Schwartz M. 2002. Autoreactive T cells induce neurotrophin production by immune and neural cells in injured rat optic nerve: Implications for protective autoimmunity. FASEB J 16:1304-1306.
5. Barrette B, Hebert MA, Filali M, Lafortune K, Vallieres N, Gowing G, Julien JP, Lacroix S. 2008. Requirement of myeloid cells for axon regeneration. J Soc Neurosci 28:9363-9376.
6. Blesch A, Tuszynski MH. 2001. GDNF gene delivery to injured adult CNS motor neurons promotes axonal growth, expression of the trophic neuropeptide CGRP, and cellular protection. J Comp Neurol 436:399-410.
7. Blesch A, Yang H, Weidner N, Hoang A, Otero D. 2004. Axonal responses to cellularly delivered NT-4/5 after spinal cord injury. Mol Cell Neurosci 27:190- 201.
8. Block ML, Zecca L, Hong JS. 2007. Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms. Nat Rev Neurosci 8:57-69.
9. Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB. 2002. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416:636-640.
10. Bsibsi M, Persoon-Deen C, Verwer RW, Meeuwsen S, Ravid R, Van Noort JM. 2006. Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators. Glia 53:688-695.
11. Busch SA, Horn KP, Silver DJ, Silver J. 2009. Overcoming macrophagemediated axonal dieback following CNS injury. J Soc Neurosci 29:9967- 9976.
12. Busch SA, Silver J. 2007. The role of extracellular matrix in CNS regeneration. Curr Opin Neurobiol 17:120-127.
13. Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, Mucke L, Johnson MH, Sofroniew MV. 1999. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23:297-308.
14. Cai D, Shen Y, De Bellard M, Tang S, Filbin MT. 1999. Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron 22:89-101.
15. Carlson SL, Parrish ME, Springer JE, Doty K, Dossett L. 1998. Acute inflammatory response in spinal cord following impact injury. Exp Neurol 151:77-88.
16. Carro E, Trejo JL, Nunez A, Torres-Aleman I. 2003. Brain repair and neuroprotection by serum insulin-like growth factor I. Mol Neurobiol 27:153-162.
17. Chen J, Joon Lee H, Jakovcevski I, Shah R, Bhagat N, Loers G, Liu HY, Meiners S, Taschenberger G, Kugler S, et al. 2010. The extracellular matrix glycoprotein tenascin-C is beneficial for spinal cord regeneration. Mol Ther 18:1769-1777.
18. Condic ML. 2001. Adult neuronal regeneration induced by transgenic integrin expression. J Neurosci 21:4782-4788.
19. Cox TR, Bird D, Baker AM, Barker HE, Ho MW, Lang G, Erler JT. 2013. LOXmediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res 73:1721-1732.
20. Cramer SC, Chopp M. 2000. Recovery recapitulates ontogeny. Trends Neurosci 23:265-271.
21. Cusimano M, Biziato D, Brambilla E, Donega M, Alfaro-Cervello C, Snider S, Salani G, Pucci F, Comi G, Garcia-Verdugo JM, et al. 2012. Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord. Brain 135:447-460.
22. David S, Aguayo AJ. 1981. Axonal elongation into peripheral nervous system "bridges" after central nervous system injury in adult rats. Science 214:931-933.
23. David S, Bouchard C, Tsatas O, Giftochristos N. 1990. Macrophages can modify the nonpermissive nature of the adult mammalian central nervous system. Neuron 5:463-469.
24. Davies JE, Tang X, Denning JW, Archibald SJ, Davies SJ. 2004. Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. Eur J Neurosci 19:1226-1242.
25. Dickendesher TL, Baldwin KT, Mironova YA, Koriyama Y, Raiker SJ, Askew KL, Wood A, Geoffroy CG, Zheng B, Liepmann CD, et al. 2012. NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nature Neurosci 15:703-712.
26. Dougherty KD, Dreyfus CF, Black IB. 2000. Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury. Neurobiol Dis 7:574-585.
27. Dusart I, Schwab ME. 1994. Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J Neurosci 6:712- 724.
28. Dvorak HF. 1986. Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650-1659.
29. Ebert S, Schoeberl T, Walczak Y, Stoecker K, Stempfl T, Moehle C, Weber BH, Langmann T. 2008. Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype. J Leukoc Biol 84:736-740.
30. Egawa M, Mukai K, Yoshikawa S, Iki M, Mukaida N, Kawano Y, Minegishi Y, Karasuyama H. 2013. Inflammatory monocytes recruited to allergic skin acquire an anti-inflammatory M2 phenotype via basophil-derived interleukin-4. Immunity 38:570-580.
31. Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV. 2004. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24:2143-2155.
32. Fisher D, Xing B, Dill J, Li H, Hoang HH, Zhao Z, Yang XL, Bachoo R, Cannon S, Longo FM, et al. 2011. Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors. J Neurosci 31:14051-14066.
33. Fujimoto T, Kawashima H, Tanaka T, Hirose M, Toyama-Sorimachi N, Matsuzawa Y, Miyasaka M. 2001. CD44 binds a chondroitin sulfate proteoglycan, aggrecan. Int Immunol 13:359-366.
34. Galea I, Bechmann I, Perry VH. 2007. What is immune privilege (not)? Trends Immunol 28:12-18.
35. Galtrey CM, Fawcett JW. 2007. The role of chondroitin sulfate proteoglycans in regeneration and plasticity in the central nervous system. Brain Res Rev 54: 1-18.
36. Giger RJ, Hollis ER, 2nd, Tuszynski MH. 2010. Guidance molecules in axon regeneration. Cold Spring Harbor Perspect Biol 2:a001867.
37. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, et al. 2010. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841- 845.
38. Goldshmit Y, McLenachan S, Turnley A. 2006. Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Res Rev 52:327-345.
39. Goritz C, Dias DO, Tomilin N, Barbacid M, Shupliakov O, Frisen J. 2011. A pericyte origin of spinal cord scar tissue. Science 333:238-242.
40. Grimpe B, Silver J. 2004. 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.
41. Gris D, Marsh DR, Oatway MA, Chen Y, Hamilton EF, Dekaban GA, Weaver LC. 2004. Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci 24:4043-4051.
42. Hanisch UK, Kettenmann H. 2007. Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387- 1394.
43. Hata K, Fujitani M, Yasuda Y, Doya H, Saito T, Yamagishi S, Mueller BK, Yamashita T. 2006. RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J Cell Biol 173:47-58.
44. Hirose J, Kawashima H, Yoshie O, Tashiro K, Miyasaka M. 2001. Versican interacts with chemokines and modulates cellular responses. J Biol Chem 276:5228-5234.
45. Horn KP, Busch SA, Hawthorne AL, van Rooijen N, Silver J. 2008. Another barrier to regeneration in the CNS: Activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. J Neurosci 28:9330-9341.
46. Johnson GB, Brunn GJ, Kodaira Y, Platt JL. 2002. Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Tolllike receptor 4. J Immunol 168:5233-5239.
47. Jones LL, Margolis RU, Tuszynski MH. 2003. The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp Neurol 182:399-411.
48. Jones LL, Yamaguchi Y, Stallcup WB, Tuszynski MH. 2002. NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. J Neurosci 22:2792-2803.
49. Jung S, Schwartz M. 2012. Non-identical twins-microglia and monocytederived macrophages in acute injury and autoimmune inflammation. Front Immunol 3:89.
50. Kaneko S, Iwanami A, Nakamura M, Kishino A, Kikuchi K, Shibata S, Okano HJ, Ikegami T, Moriya A, Konishi O, et al. 2006. A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nature medicine 12:1380-1389.
51. Kantor DB, Chivatakarn O, Peer KL, Oster SF, Inatani M, Hansen MJ, Flanagan JG, Yamaguchi Y, Sretavan DW, Giger RJ, et al. 2004. Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans. Neuron 44:961-975.
52. Kawashima H, Hirose M, Hirose J, Nagakubo D, Plaas AH, Miyasaka M. 2000. Binding of a large chondroitin sulfate/dermatan sulfate proteoglycan, versican, to L-selectin, P-selectin, and CD44. J Biol Chem 275:35448-35456.
53. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. 2009. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 29:13435-13444.
54. Kigerl KA, Lai W, Rivest S, Hart RP, Satoskar AR, Popovich PG. 2007. Toll-like receptor (TLR)22 and TLR-4 regulate inflammation, gliosis, and myelin sparing after spinal cord injury. J Neurochem 102:37-50.
55. Kobayashi NR, Fan DP, Giehl KM, Bedard AM, Wiegand SJ, Tetzlaff W. 1997. BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Talpha1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 17:9583-9595.
56. Kokaia Z, Martino G, Schwartz M, Lindvall O. 2012. Cross-talk between neural stem cells and immune cells: The key to better brain repair? Nat Neurosci 15:1078-1087.
57. Kunis G, Baruch K, Rosenzweig N, Kertser A, Miller O, Berkutzki T, Schwartz M. 2013. IFN-gamma-dependent activation of the brain's choroid plexus for CNS immune surveillance and repair. Brain 136:3427-3440.
58. Kurimoto T, Yin Y, Habboub G, Gilbert HY, Li Y, Nakao S, Hafezi-Moghadam A, Benowitz LI. 2013. Neutrophils express oncomodulin and promote optic nerve regeneration. J Neurosci 33:14816-14824.
59. Laflamme N, Rivest S. 2001. Toll-like receptor 4: The missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components. FASEB J 15:155-163.
60. Lazarov-Spiegler O, Solomon AS, Zeev-Brann AB, Hirschberg DL, Lavie V, Schwartz M. 1996. Transplantation of activated macrophages overcomes central nervous system regrowth failure. FASEB J 10:1296-1302.
61. Leibinger M, Muller A, Andreadaki A, Hauk TG, Kirsch M, Fischer D. 2009. Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor. J Neurosci 29:14334-14341.
62. Leon S, Yin Y, Nguyen J, Irwin N, Benowitz LI. 2000. Lens injury stimulates axon regeneration in the mature rat optic nerve. J Neurosci 20:4615-4626.
63. Liu X, Hawkes E, Ishimaru T, Tran T, Sretavan DW. 2006. EphB3: An endogenous mediator of adult axonal plasticity and regrowth after CNS injury. J Neurosci 26:3087-3101.
64. Logan A, Baird A, Berry M. 1999. Decorin attenuates gliotic scar formation in the rat cerebral hemisphere. Exp Neurol 159:504-510.
65. London A, Itskovich E, Benhar I, Kalchenko V, Mack M, Jung S, Schwartz M. 2011. Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J Exp Med 208:23-39.
66. Ma Y, Li J, Chiu I, Wang Y, Sloane JA, Lu J, Kosaras B, Sidman RL, Volpe JJ, Vartanian T. 2006. Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. J Cell Biol 175:209- 215.
67. Martinez FO, Gordon S, Locati M, Mantovani A. 2006. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: New molecules and patterns of gene expression. J Immunol 177:7303-7311.
68. Martino G, Pluchino S, Bonfanti L, Schwartz M. 2011. Brain regeneration in physiology and pathology: The immune signature driving therapeutic plasticity of neural stem cells. Physiol Rev 91:1281-1304.
69. Matsunaga E, Nakamura H, Chedotal A. 2006. Repulsive guidance molecule plays multiple roles in neuronal differentiation and axon guidance. J Neurosci 26:6082-6088.
70. McKeon RJ, Hoke A, Silver J. 1995. Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp Neurol 136:32-43.
71. McKeon RJ, Schreiber RC, Rudge JS, Silver J. 1991. 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.
72. Midwood K, Sacre S, Piccinini AM, Inglis J, Trebaul A, Chan E, Drexler S, Sofat N, Kashiwagi M, Orend G, et al. 2009. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat Med 15:774-780.
73. Midwood KS, Orend G. 2009. The role of tenascin-C in tissue injury and tumorigenesis. J Cell Commun Signal 3:287-310.
74. Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M. 1999. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5:49-55.
75. Monnier PP, Sierra A, Macchi P, Deitinghoff L, Andersen JS, Mann M, Flad M, Hornberger MR, Stahl B, Bonhoeffer F, et al. 2002. RGM is a repulsive guidance molecule for retinal axons. Nature 419:392-395.
76. Moon LD, Asher RA, Rhodes KE, Fawcett JW. 2001. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nat Neurosci 4:465-466.
77. Muller A, Hauk TG, Fischer D. 2007. Astrocyte-derived CNTF switches mature RGCs to a regenerative state following inflammatory stimulation. Brain 130: 3308-3320.
78. Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, Yamane J, Yoshimura A, Iwamoto Y, Toyama Y, et al. 2006. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 12:829-834.
79. Okamura Y, Watari M, Jerud ES, Young DW, Ishizaka ST, Rose J, Chow JC, Strauss JF, 3rd. 2001. The extra domain A of fibronectin activates Toll-like receptor 4. J Biol Chem 276:10229-10233.
80. Popovich PG, Guan Z, McGaughy V, Fisher L, Hickey WF, Basso DM. 2002. The neuropathological and behavioral consequences of intraspinal microglial/ macrophage activation. J Neuropathol Exp Neurol 61:623-633.
81. Popovich PG, Guan Z, Wei P, Huitinga I, van Rooijen N, Stokes BT. 1999. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol 158:351-365.
82. Ramer MS, Priestley JV, McMahon SB. 2000. Functional regeneration of sensory axons into the adult spinal cord. Nature 403:312-316.
83. Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, et al. 1998. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 4:814-821.
84. Rolls A, Avidan H, Cahalon L, Schori H, Bakalash S, Litvak V, Lev S, Lider O, Schwartz M. 2004. A disaccharide derived from chondroitin sulphate proteoglycan promotes central nervous system repair in rats and mice. Eur J Neurosci 20:1973-1983.
85. Rolls A, Shechter R, London A, Segev Y, Jacob-Hirsch J, Amariglio N, Rechavi G, Schwartz M. 2008. Two faces of chondroitin sulfate proteoglycan in spinal cord repair: A role in microglia/macrophage activation. PLoS Med 5: e171.
86. Rolls A, Shechter R, London A, Ziv Y, Ronen A, Levy R, Schwartz M. 2007. Toll-like receptors modulate adult hippocampal neurogenesis. Nat Cell Biol 9:1081-1088.
87. Rolls A, Shechter R, Schwartz M. 2009. The bright side of the glial scar in CNS repair. Nat Rev Neurosci 10:235-241.
88. Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke JP, et al. 1996. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675-686.
89. Schnell L, Schneider R, Kolbeck R, Barde YA, Schwab ME. 1994. Neurotrophin- 3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature 367:170-173.
90. Schnell L, Schwab ME. 1990. Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 343:269-272.
91. Schwab JM, Conrad S, Monnier PP, Julien S, Mueller BK, Schluesener HJ. 2005. Spinal cord injury-induced lesional expression of the repulsive guidance molecule (RGM). Eur J Neurosci 21:1569-1576.
92. Schwartz M, Baruch K. 2014. The resolution of neuroinflammation in neurodegeneration: Leukocyte recruitment via the choroid plexus. EMBO J 33:7-22.
93. Schwartz M, Shechter R. 2010. Systemic inflammatory cells fight off neurodegenerative disease. Nat Rev Neurol 6:405-410.
94. Schwartz M, Yoles E. 2006. Immune-based therapy for spinal cord repair: Autologous macrophages and beyond. J Neurotrauma 23:360-370.
95. Sharma K, Selzer ME, Li S. 2012. Scar-mediated inhibition and CSPG receptors in the CNS. Exp Neurol 237:370-378.
96. Shechter R, London A, Schwartz M. 2013a. Orchestrated leukocyte recruitment to immune-privileged sites: Absolute barriers versus educational gates. Nat Rev Immunol 13:206-218.
97. Shechter R, London A, Varol C, Raposo C, Cusimano M, Yovel G, Rolls A, Mack M, Pluchino S, Martino G, et al. 2009. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med 6:e1000113.
98. Shechter R, Miller O, Yovel G, Rosenzweig N, London A, Ruckh J, Kim KW, Klein E, Kalchenko V, Bendel P, et al. 2013b. Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity 38:555-569.
99. Shechter R, Raposo C, London A, Sagi I, Schwartz M. 2011. The glial scar- monocyte interplay: A pivotal resolution phase in spinal cord repair. PLoS One 6:e27969.
100. Shechter R, Schwartz M. 2013a. CNS sterile injury: Just another wound healing? Trends Mol Med 19:135-143.
101. Shechter R, Schwartz M. 2013b. Harnessing monocyte-derived macrophages to control central nervous system pathologies: No longer 'if' but 'how'. J Pathol 229:332-346.
102. Shen Y, Tenney AP, Busch SA, Horn KP, Cuascut FX, Liu K, He Z, Silver J, Flanagan JG. 2009. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 326:592-596.
103. Sherman LS, Back SA. 2008. A 'GAG' reflex prevents repair of the damaged CNS. Trends Neurosci 31:44-52.
104. Silver J, Miller JH. 2004. Regeneration beyond the glial scar. Nat Rev Neurosci 5:146-156.
105. Stirling DP, Liu S, Kubes P, Yong VW. 2009. Depletion of Ly6G/Gr-1 leukocytes after spinal cord injury in mice alters wound healing and worsens neurological outcome. J Neurosci 29:753-764.
106. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon JC. 2002. Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med 195:99-111.
107. Vo T, Carulli D, Ehlert EM, Kwok JC, Dick G, Mecollari V, Moloney EB, Neufeld G, de Winter F, Fawcett JW, et al. 2013. The chemorepulsive axon guidance protein semaphorin3A is a constituent of perineuronal nets in the adult rodent brain. Mol Cell Neurosci 56C:186-200.
108. Yeo TK, Brown L, Dvorak HF. 1991. Alterations in proteoglycan synthesis common to healing wounds and tumors. Am J Pathol 138:1437-1450.
109. Yin Y, Cui Q, Gilbert HY, Yang Y, Yang Z, Berlinicke C, Li Z, Zaverucha-do- Valle C, He H, Petkova V, et al. 2009. Oncomodulin links inflammation to optic nerve regeneration. Proc Natl Acad Sci USA 106:19587-19592.
110. Yin Y, Cui Q, Li Y, Irwin N, Fischer D, Harvey AR, Benowitz LI. 2003. Macrophage- derived factors stimulate optic nerve regeneration. J Neurosci 23: 2284-2293.
111. Yin Y, Henzl MT, Lorber B, Nakazawa T, Thomas TT, Jiang F, Langer R, Benowitz LI. 2006. Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat Neurosci 9:843-852.
112. Yiu G, He Z. 2006. Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 7:617-627.
113. Zhang Y, Winterbottom JK, Schachner M, Lieberman AR, Anderson PN. 1997. Tenascin-C expression and axonal sprouting following injury to the spinal dorsal columns in the adult rat. J Neurosci Res 49:433-450.
114. Zhou FQ, Walzer M, Wu YH, Zhou J, Dedhar S, Snider WD. 2006. Neurotrophins support regenerative axon assembly over CSPGs by an ECM-integrinindependent mechanism. J Cell Sci 119:2787-2796.
115. Zhou J, Nagarkatti P, Zhong Y, Nagarkatti M. 2010. Immune modulation by chondroitin sulfate and its degraded disaccharide product in the development of an experimental model of multiple sclerosis. J Neuroimmunol 223: 55-64.
116. Ziv Y, Avidan H, Pluchino S, Martino G, Schwartz M. 2006. 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.