The glial scar in spinal cord injury and repair

Neuroscience Bulletin

Volumn 29, Issue 4, 2013, Pages 421-435

  Yuan, Yi Min ^a   He, Cheng ^a  

^a SECOND MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

astrocyte activation; axonal regeneration; glial scar; neuroinflammation; reactive astrogliosis; spinal cord injury

Indexed keywords

BONE MORPHOGENETIC PROTEIN; CHONDROITIN ABC LYASE; DECORIN; EPHRIN; EPIDERMAL GROWTH FACTOR RECEPTOR; FLAVOPIRIDOL; GLIAL FIBRILLARY ACIDIC PROTEIN; INTERLEUKIN 6; MATRIX METALLOPROTEINASE; OLOMOUCINE; PROTEOCHONDROITIN SULFATE; RAPAMYCIN; ROLIPRAM; ROSE BENGAL; STAT3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TRIPTOLIDE; VIMENTIN;

ASTROCYTE; ASTROCYTOSIS; CYTOSKELETON; EXTRACELLULAR MATRIX; GLIA; GLIA SCAR; HUMAN; LOCOMOTION; LOW LEVEL LASER THERAPY; MICROGLIA; NERVE CELL PLASTICITY; NERVE FIBER GROWTH; NERVE FIBER REGENERATION; NERVE SPROUTING; NERVOUS SYSTEM INFLAMMATION; NEURAL STEM CELL; NONHUMAN; REVIEW; SCAR; SPINAL CORD HEMISECTION; SPINAL CORD INJURY;

ANIMALS; ASTROCYTES; CICATRIX; HUMANS; NERVE REGENERATION; NEUROGLIA; SPINAL CORD INJURIES;

EID: 84881136066     PISSN: 16737067     EISSN: 19958218     Source Type: Journal    
DOI: 10.1007/s12264-013-1358-3     Document Type: Review

References (137)

1. Wilhelmsson U, Bushong EA, Price DL, Smarr BL, Phung V, Terada M, et al. Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proc Natl Acad Sci U S A 2006, 103(46): 17513-17518.
2. Su Z, Yuan Y, Chen J, Zhu Y, Qiu Y, Zhu F, et al. Reactive astrocytes inhibit the survival and differentiation of oligodendrocyte precursor cells by secreted TNF-α. J Neurotrauma 2011, 28(6): 1089-1100.
3. Fawcett JW, Asher RA. The glial scar and central nervous system repair. Brain Res Bull 1999, 49(6): 377-391.
4. Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002, 416(6881): 636-640.
5. Rolls A, Shechter R, Schwartz M. The bright side of the glial scar in CNS repair. Nat Rev Neurosci 2009, 10(3): 235-241.
6. Kawano H, Kimura-Kuroda J, Komuta Y, Yoshioka N, Li HP, Kawamura K, et al. Role of the lesion scar in the response to damage and repair of the central nervous system. Cell Tissue Res 2012, 349(1): 169-180.
7. Göritz C, Dias DO, Tomilin N, Barbacid M, Shupliakov O, Frisén J. A pericyte origin of spinal cord scar tissue. Science 2011, 333(6039): 238-242.
8. Matthews MA, St Onge MF, Faciane CL, Gelderd JB. Axon sprouting into segments of rat spinal cord adjacent to the site of a previous transection. Neuropathol Appl Neurobiol 1979, 5(3): 181-196.
9. Hu R, Zhou J, Luo C, Lin J, Wang X, Li X, et al. Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury. J Neurosurg Spine 2010, 13(2): 169-180.
10. Matsui F, Oohira A. Proteoglycans and injury of the central nervous system. Congenit Anom 2004, 44: 181-188.
11. Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci 2004, 5(2): 146-156.
12. Rhodes KE, Fawcett JW. Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS? J Anat 2004, 204: 33-48.
13. Tang X, Davies JE, Davies, SJ. 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 2003, 71: 427-444.
14. Jones LL, Margolis RU, Tuszynski MH. The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp Neurol 2003, 182: 399-411.
15. Buss A, Pech K, Kakulas BA, Martin D, Schoenen J, Noth J, et al. NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury. BMC Neurol 2009, 9: 32.
16. Monnier PP, Sierra A, Schwab JM, Henke-Fahle S, Mueller BK. The Rho/RoCK pathway mediates neurite growthinhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Mol Cell Neurosci 2003, 22(3): 319-330.
17. Siebert JR, Osterhout DJ. The inhibitory effects of chondroitin sulfate proteoglycans on oligodendrocytes. J Neurochem 2011, 119(1): 176-188.
18. Rolls A, Shechter R, London A, Segev Y, Jacob-Hirsch J, Amariglio N, et al. Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med 2008, 5(8): e171.
19. Malhotra SK, Svensson M, Aldskogius H, Bhatnagar R, Das GD, Shnitka TK. Diversity among reactive astrocytes: proximal reactive astrocytes in lacerated spinal cord preferentially react with monoclonal antibody J1-31. Brain Res Bull 1993, 30(3-4): 395-404.
20. Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, et al. Genomic analysis of reactive astrogliosis. J Neurosci 2012, 32(18): 6391-6410.
21. Buffo A, Rite I, Tripathi P, Lepier A, Colak D, Horn AP, et al. Origin and progeny of reactive gliosis: a source of multipotent cells in the injured brain. Proc Natl Acad Sci U S A 2008, 105: 3581-3586.
22. Renault-Mihara F, Okada S, Shibata S, Nakamura M, Toyama Y, Okano H. Spinal cord injury: emerging beneficial role of reactive astrocytes' migration. Int J Biochem Cell Biol 2008, 40(9): 1649-1653.
23. Guo F, Maeda Y, Ma J, Delgado M, Sohn J, Miers L, et al. Macroglial plasticity and the origins of reactive astroglia in experimental autoimmune encephalomyelitis. J Neurosci 2011, 31(33): 11914-11928.
24. Horky LL, Galimi F, Gage FH, Horner PJ. Fate of endogenous stem/progenitor cells following spinal cord injury. J Comp Neurol 2006, 498: 525-538.
25. Lytle JM, Wrathall JR. Glial cell loss, proliferation and replacement in the contused murine spinal cord. Eur J Neurosci 2007, 25: 1711-1724.
26. Decimo I, Bifari F, Rodriguez FJ, Malpeli G, Dolci S, Lavarini V, et al. Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction. Stem Cells 2011, 29(12): 2062-2076.
27. Meletis K, Barnabé-Heider F, Carlén M, Evergren E, Tomilin N, Shupliakov O, et al. Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biol 2008, 6(7): e182.
28. Sellers DL, Maris DO, Horner PJ. Postinjury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury. J Neurosci 2009, 29(20): 6722-6733.
29. Horner PJ, Power AE, Kempermann G, Kuhn HG, Palmer TD, Winkler J, et al. Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J Neurosci 2000, 20(6): 2218-2228.
30. Barnabé-Heider F, Göritz C, Sabelström H, Takebayashi H, Pfrieger FW, Meletis K, et al. Origin of new glial cells in intact and injured adult spinal cord. Cell Stem Cell 2010, 7: 470-482.
31. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, et al. Identification of a neural stem cell in the adult mammalian central nervous system. Cell 1999, 96(1): 25-34.
32. Fox K, Caterson B. Neuroscience. Freeing the brain from the perineuronal net. Science 2002, 298: 1187-1189.
33. McTigue DM, Wei P, Stokes BT. Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. J Neurosci 2001, 21: 3392-3400.
34. Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 2010, 468(7323): 562-566.
35. McTigue DM, Tripathi R, Wei P. NG2 colocalizes with axons and is expressed by a mixed cell population in spinal cord lesions. J Neuropathol Exp Neurol 2006, 65: 406-420.
36. Shearer MC, Niclou SP, Brown D, Asher RA, Holtmaat AJ, Levine JM, et al. The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which can be overcome by manipulation of inhibitory molecules or axonal signalling pathways. Mol Cell Neurosci 2003, 24(4): 913-925.
37. Jones LL, Yamaguchi Y, Stallcup WB, Tuszynski MH. NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. J Neurosci 2002, 22: 2792-2803.
38. Zhu L, Xiang P, Guo K, Wang A, Lu J, Tay SS, et al. Microglia/monocytes with NG2 expression have no phagocytic function in the cortex after LPS focal injection into the rat brain. Glia 2012, 60(9): 1417-1426.
39. Mamaeva D, Ripoll C, Bony C, Teigell M, Perrin FE, Rothhut B, et al. Isolation of mineralizing Nestin+ Nkx6.1+ vascular muscular cells from the adult human spinal cord. BMC Neurosci 2011, 12: 99.
40. de Castro R Jr, Tajrishi R, Claros J, Stallcup WB. Differential responses of spinal axons to transection: influence of the NG2 proteoglycan. Exp Neurol 2005, 192(2): 299-309.
41. Moransard M, Dann A, Staszewski O, Fontana A, Prinz M, Suter T. NG2 expressed by macrophages and oligodendrocyte precursor cells is dispensable in experimental autoimmune encephalomyelitis. Brain 2011, 134(Pt 5): 1315-1330.
42. Matsuura I, Taniguchi J, Hata K, Saeki N, Yamashita T. BMP inhibition enhances axonal growth and functional recovery after spinal cord injury. J Neurochem 2008, 105: 1471-1479.
43. Xiao Q, Du Y, Wu W, Yip HK. Bone morphogenetic proteins mediate cellular response and, together with Noggin, regulate astrocyte differentiation after spinal cord injury. Exp Neurol 2010, 221(2): 353-366.
44. Sahni V, Mukhopadhyay A, Tysseling V, Hebert A, Birch D, McGuire TL, et al. BMPR1a and BMPR1b signaling exert opposing effects on gliosis after spinal cord injury. J Neurosci 2010, 30: 1839-1855.
45. Duchossoy Y, Horvat JC, Stettler O. MMP-related gelatinase activity is strongly induced in scar tissue of injured adult spinal cord and forms pathways for ingrowing neurites. Mol Cell Neurosci 2001, 17(6): 945-956.
46. Zhang H, Chang M, Hansen CN, Basso DM, Noble-Haeusslein LJ. Role of matrix metalloproteinases and therapeutic benefits of their inhibition in spinal cord injury. Neurotherapeutics 2011, 8(2): 206-220.
47. Hsu JY, Bourguignon LY, Adams CM, Peyrollier K, Zhang H, Fandel T, et al. Matrix metalloproteinase-9 facilitates glial scar formation in the injured spinal cord. J Neurosci 2008, 28(50): 13467-13877.
48. Pizzi MA, Crowe MJ. Transplantation of fibroblasts that overexpress matrix metalloproteinase-3 into the site of spinal cord injury in rats. J Neurotrauma 2006, 23(12): 1750-1765.
49. Planas AM, Justicia C, Soriano MA, Ferrer I. Epidermal growth factor receptor in proliferating reactive glia following transient focal ischemia in the rat brain. Glia 1998, 23(2): 120-129.
50. Codeluppi S, Svensson Ci, Hefferan MP, Valencia F, Silldorff MD, Oshiro M, et al. The Rheb-mToR pathway is upregulated in reactive astrocytes of the injured spinal cord. J Neurosci 2009, 29(4): 1093-1104.
51. White RE, Rao M, Gensel JC, McTigue DM, Kaspar BK, Jakeman LB. Transforming growth factor α transforms astrocytes to a growth-supportive phenotype after spinal cord injury. J Neurosci 2011, 31(42): 15173-15187.
52. Liu B, Neufeld AH. Activation of epidermal growth factor receptor causes astrocytes to form cribriform structures. Glia 2004, 46: 153-168.
53. Qu WS, Tian DS, Guo ZB, Fang J, Zhang Q, Yu ZY, et al. Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the associated secondary damage in rats after spinal cord injury. J Neuroinflammation 2012, 9: 178.
54. Goldshmit Y, McLenachan S, Turnley A. Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Res Rev 2006, 52: 327-345.
55. Bundesen LQ, Scheel TA, Bregman BS, Kromer LF. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci 2003, 23(21): 7789-7800.
56. Fabes J, Anderson P, Yáñez-Muñoz RJ, Thrasher A, Brennan C, Bolsover S. Accumulation of the inhibitory receptor EphA4 may prevent regeneration of corticospinal tract axons following lesion. Eur J Neurosci 2006, 23(7): 1721-1730.
57. Goldshmit Y, Galea MP, Wise G, Bartlett PF, Turnley AM. Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice. J Neurosci 2004, 24(45): 10064-10073.
58. Herrmann JE, Shah RR, Chan AF, Zheng B. EphA4 deficient mice maintain astroglial-fibrotic scar formation after spinal cord injury. Exp Neurol 2010, 223(2): 582-598.
59. Dixon KJ, Munro KM, Boyd AW, Bartlett PF, Turnley AM. Partial change in EphA4 knockout mouse phenotype: loss of diminished GFAP upregulation following spinal cord injury. Neurosci Lett 2012, 525(1): 66-71.
60. Baldwin SA, Broderick R, Blades DA, Scheff SW. Alterations in temporal/spatial distribution of GFAP- and vimentinpositive astrocytes after spinal cord contusion with the New York University spinal cord injury device. Neurotrauma 1998, 15(12): 1015-1026.
61. Pekny M, Johansson CB, Eliasson C, Stakeberg J, Wallén A, Perlmann T, et al. Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J Cell Biol 1999, 145(3): 503-514.
62. Lepekhin EA, Eliasson C, Berthold CH, Berezin V, Bock E, Pekny M. Intermediate filaments regulate astrocyte motility. J Neurochem 2001, 79(3): 617-625.
63. Ribotta MG, Menet V, Privat A. Glial scar and axonal regeneration in the CNS: lessons from GFAP and vimentin transgenic mice. Acta Neurochir Suppl 2004, 89: 87-92.
64. Menet V, Prieto M, Privat A, Giménez y Ribotta M. Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes. Proc Natl Acad Sci U S A 2003, 100(15): 8999-9004.
65. Wang X, Chen W, Liu W, Wu J, Shao Y, Zhang X. The role of thrombospondin-1 and transforming growth factor-beta after spinal cord injury in the rat. Clin Neurosci 2009, 16(6): 818-821.
66. Buss A, Pech K, Kakulas BA, Martin D, Schoenen J, Noth J, et al. TGF-beta1 and TGF-beta2 expression after traumatic human spinal cord injury. Spinal Cord 2008, 46(5): 364-731.
67. Kohta M, Kohmura E, Yamashita T. Inhibition of TGFbeta1 promotes functional recovery after spinal cord injury. Neurosci Res 2009, 65(4): 393-401.
68. Lagord C, Berry M, Logan A. Expression of TGFbeta2 but not TGFbeta1 correlates with the deposition of scar tissue in the lesioned spinal cord. Mol Cell Neurosci 2002, 20(1): 69-92.
69. Dominguez E, Mauborgne A, Mallet J, Desclaux M, Pohl M. SOCS3-mediated blockade of JAK/STAT3 signaling pathway reveals its major contribution to spinal cord neuroinflammation and mechanical allodynia after peripheral nerve injury. J Neurosci 2010, 30(16): 5754-5766.
70. Dziennis S, Alkayed NJ. Role of signal transducer and activator of transcription 3 in neuronal survival and regeneration. Rev Neurosci 2008, 19(4-5): 341-361.
71. Herrmann JE, Imura T, Song B, Qi J, Ao Y, Nguyen TK, et al. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 2008, 28(28): 7231-7243.
72. Tsuda M, Kohro Y, Yano T, Tsujikawa T, Kitano J, Tozaki-Saitoh H, et al. JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. Brain 2011, 134(Pt 4): 1127-1139.
73. Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, et al. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 2006, 12(7): 829-834.
74. Regis G, Pensa S, Boselli D, Novelli F, Poli V. Ups and downs: the STAT1:STAT3 seesaw of interferon and gp130 receptor signalling. Semin Cell Dev Biol 2008, 19(4): 351-359.
75. Gris P, Tighe A, Levin D, Sharma R, Brown A. Transcriptional regulation of scar gene expression in primary astrocytes. Glia 2007, 55(11): 1145-1155.
76. Kirsch M, Trautmann N, Ernst M, Hofmann HD. Involvement of gp130-associated cytokine signaling in Müller cell activation following optic nerve lesion. Glia 2010, 58(7): 768-779.
77. Ye J, Cao L, Cui R, Huang A, Yan Z, Lu C, et al. The effects of ciliary neurotrophic factor on neurological function and glial activity following contusive spinal cord injury in the rats. Brain Res 2004, 997(1): 30-39.
78. Okada S, Nakamura M, Mikami Y, Shimazaki T, Mihara M, Ohsugi Y, et al. Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury. J Neurosci Res 2004, 76(2): 265-276.
79. Fang Z, Duthoit N, Wicher G, Källskog O, Ambartsumian N, Lukanidin E, et al. Intracellular calcium-binding protein S100A4 influences injury-induced migration of white matter astrocytes. Acta Neuropathol 2006, 111(3): 213-219.
80. McKillop WM, Dragan M, Schedl A, Brown A. Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury. Glia 2013, 61(2): 164-177.
81. Sivasankaran R, Pei J, Wang KC, Zhang YP, Shields CB, Xu XM, et al. PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nat Neurosci 2004, 7(3): 261-268.
82. Bhalala OG, Pan L, Sahni V, McGuire TL, Gruner K, Tourtellotte WG, et al. microRNA-21 regulates astrocytic response following spinal cord injury. J Neurosci 2012 32(50): 17935-17947.
83. Karimi-Abdolrezaee S, Billakanti R. Reactive Astrogliosis after Spinal Cord injury-Beneficial and Detrimental Effects. Mol Neurobiol 2012, 46(2): 251-264.
84. Gervasi NM, Kwok JC, Fawcett JW. Role of extracellular factors in axon regeneration in the CNS: implications for therapy. Regen Med 2008, 3(6): 907-923.
85. Yiu G, He Z. Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 2006, 7(8): 617-627.
86. Cafferty WB, McGee AW, Strittmatter SM. Axonal growth therapeutics: regeneration or sprouting or plasticity? Trends Neurosci 2008, 31(5): 215-220.
87. Sharma K, Selzer ME, Li S. Scar-mediated inhibition and CSPG receptors in the CNS. Exp Neurol 2012, 237(2): 370-378.
88. Clark LD, Clark RK, Heber-Katz E. A new murine model for mammalian wound repair and regeneration. Clin immunol immunopathol 1998, 88: 35-45.
89. Li X, Gu W, Masinde G, Hamilton-Ulland M, Xu S, Mohan S, et al. Genetic control of the rate of wound healing in mice. Heredity 2001, 86: 668-674.
90. Kostyk SK, Popovich PG, Stokes BT, Wei P, Jakeman LB. Robust axonal growth and a blunted macrophage response are associated with impaired functional recovery after spinal cord injury in the MRL/MpJ mouse. Neuroscience 2008, 156(3): 498-514.
91. Thuret S, Thallmair M, Horky LL, Gage FH. Enhanced functional recovery in MRL/MpJ mice after spinal cord dorsal hemisection. PLoS One 2012, 7(2): e30904.
92. Frisén J, Haegerstrand A, Risling M, Fried K, Johansson CB, Hammarberg H, et al. Spinal axons in central nervous system scar tissue are closely related to lamininimmunoreactive astrocytes. Neuroscience 1995, 65(1): 293-304.
93. King VR, Henseler M, Brown RA, Priestley JV. Mats made from fibronectin support oriented growth of axons in the damaged spinal cord of the adult rat. Exp Neurol 2003, 182(2): 383-398.
94. Morgenstern DA, Asher RA, Fawcett JW. Chondroitin sulphate proteoglycans in the CNS injury response. Prog Brain Res 2002, 137: 313-332.
95. Shen Y, Tenney A, Busch SA, Horn KP, Cuascut FX, Liu K, et al. PTP sigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 2009, 326(5952): 592-596.
96. Fry EJ, Chagnon MJ, López-Vales R, Tremblay ML, David S. Corticospinal tract regeneration after spinal cord injury in receptor protein tyrosine phosphatase sigma deficient mice. Glia 2010, 58(4): 423-433.
97. Fisher D, Xing B, Dill J, Li H, Hoang HH, Zhao Z, et al. Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors. J Neurosci 2011, 31(40): 14051-14066.
98. Inman DM, Steward O. Physical size does not determine the unique histopathological response seen in the injured mouse spinal cord. J Neurotrauma 2003, 20(1): 33-42.
99. Sroga JM, Jones TB, Kigerl KA, McGaughy VM, Popovich PG. Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol 2003, 462(2): 223-240.
100. Takigawa T, Yonezawa T, Yoshitaka T, Minaguchi J, Kurosaki M, Tanaka M, et al. Separation of the perivascular basement membrane provides a conduit for inflammatory cells in a mouse spinal cord injury model. J Neurotrauma 2010, 27(4): 739-751.
101. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 2009, 29: 13435-13444.
102. Shechter R, Raposo C, London A, Sagi I, Schwartz M. The glial scar-monocyte interplay: a pivotal resolution phase in spinal cord repair. PLoS One 2011, 6(12): e27969.
103. Raslan AM, Nemecek AN. Controversies in the surgical management of spinal cord injuries. Neurol Res int 2012, 2012: 417834.
104. Anghelescu N, Petrescu A, Alexandrescu I. Therapy study on the experimental injury of spinal cord. iV. High doses of methyl-prednisolone. Rom J Neurol Psychiatry 1995, 33(3-4): 241-249.
105. Rochkind S, Ouaknine GE. New trend in neuroscience: lowpower laser effect on peripheral and central nervous system (basic science, preclinical and clinical studies). Neurol Res 1992, 14(1): 2-11.
106. Zhang SX, Geddes JW, Owens JL, Holmberg EG. X-irradiation reduces lesion scarring at the contusion site of adult rat spinal cord. Histol Histopathol 2005, 20(2): 519-530.
107. Ridet JL, Pencalet P, Belcram M, Giraudeau B, Chastang C, Philippon J, et al. Effects of spinal cord X-irradiation on the recovery of paraplegic rats. Exp Neurol 2000, 161(1): 1-14.
108. Moriarty LJ, Borgens RB. An oscillating extracellular voltage gradient reduces the density and influences the orientation of astrocytes in injured mammalian spinal cord. J Neurocytol 2001, 30(1): 45-57.
109. Shapiro S, Borgens R, Pascuzzi R, Roos K, Groff M, Purvines S, et al. Oscillating field stimulation for complete spinal cord injury in humans: a phase 1 trial. J Neurosurg Spine 2005, 2(1): 3-10.
110. Fassbender JM, Whittemore SR, Hagg T. Targeting microvasculature for neuroprotection after SCi. Neurotherapeutics 2011, 8(2): 240-251.
111. Carter LM, Starkey ML, Akrimi SF, Davies M, McMahon SB, Bradbury EJ, et al. The yellow fluorescent protein (YFP-H) mouse reveals neuroprotection as a novel mechanism underlying chondroitinase ABC-mediated repair after spinal cord injury. J Neurosci 2008, 28(52): 14107-14120.
112. Bartus K, James ND, Bosch KD, Bradbury EJ. Chondroitin sulphate proteoglycans: Key modulators of spinal cord and brain plasticity. Exp Neurol 2012, 235: 5-17.
113. Kilcoyne M, Sharma S, McDevitt N, O'Leary C, Joshi L, McMahon SS. Neuronal glycosylation differentials in normal, injured and chondroitinase- treated environments. Biochem Biophys Res Commun 2012, 420(3): 616-622.
114. Onose G, Anghelescu A, Muresanu DF, Padure L, Haras MA, Chendreanu CO, et al. A review of published reports on neuroprotection in spinal cord injury. Spinal Cord 2009, 47(10): 716-726.
115. Bradbury EJ, Carter LM. Manipulating the glial scar: chondroitinase ABC as a therapy for spinal cord injury. Brain Res Bull 2011, 84(4-5): 306-316.
116. Zuo J, Ferguson TA, Hernandez YJ, Stetler-Stevenson WG, Muir D. Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan. J Neurosci 1998, 18(14): 5203-5211.
117. Busch SA, Hamilton JA, Horn KP, Cuascut FX, Cutrone R, Lehman N, et al. Multipotent adult progenitor cells prevent macrophage-mediated axonal dieback and promote regrowth after spinal cord injury. J Neurosci 2011, 31(3): 944-953.
118. 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 2004, 24(6): 1393-1397.
119. Davies JE, Tang X, Denning JW, Archibald SJ, Davies SJ. Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. Eur J Neurosci 2004, 19(5): 1226-1242.
120. Logan A, Baird A, Berry M. Decorin attenuates gliotic scar formation in the rat cerebral hemisphere. Exp Neurol 1999, 159: 504-510.
121. Davies JE, Tang X, Bournat JC, Davies SJ. Decorin promotes plasminogen/plasmin expression within acute spinal cord injuries and by adult microglia in vitro. J Neurotrauma 2006, 23(3-4): 397-408.
122. Minor K, Tang X, Kahrilas G, Archibald SJ, Davies JE, Davies SJ. Decorin promotes robust axon growth on inhibitory CSPGs and myelin via a direct effect on neurons. Neurobiol Dis 2008, 32(1): 88-95.
123. Beal MF. Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci 2000, 23: 298-304.
124. Hausmann ON, Fouad K, Wallimann T, Schwab ME. Protective effects of oral creatine supplementation on spinal cord injury in rats. Spinal Cord 2002, 40(9): 449-456.
125. Kao KK, Fink MP. The biochemical basis for the antiinflammatory and cytoprotective actions of ethyl pyruvate and related compounds. Biochem Pharmacol 2010, 80(2): 151-159.
126. Yuan Y, Su Z, Pu Y, Liu X, Chen J, Zhu F, et al. Ethyl pyruvate promotes spinal cord repair by ameliorating the glial microenvironment. Br J Pharmacol 2012, 166(2): 749-763.
127. Wu J, Stoica BA, Faden AI. Cell cycle activation and spinal cord injury. Neurotherapeutics 2011, 8(2): 221-228.
128. Tian DS, Yu ZY, Xie MJ, Bu BT, Witte OW, Wang W. Suppression of astroglial scar formation and enhanced axonal regeneration associated with functional recovery in a spinal cord injury rat model by the cell cycle inhibitor olomoucine. J Neurosci Res 2006, 84(5): 1053-1063.
129. Tian DS, Xie MJ, Yu ZY, Zhang Q, Wang YH, Chen B, et al. Cell cycle inhibition attenuates microglia induced inflammatory response and alleviates neuronal cell death after spinal cord injury in rats. Brain Res 2007, 1135(1): 177-185.
130. Byrnes KR, Stoica BA, Fricke S, Di Giovanni S, Faden AI. Cell cycle activation contributes to post-mitotic cell death and secondary damage after spinal cord injury. Brain 2007, 130(Pt 11): 2977-2992.
131. Kabadi SV, Stoica BS, Hanscom M, Loane DJ, Kharebava G, Murray MG, et al. CR8, a selective and potent CDK inhibitor, provides neuroprotection in experimental traumatic brain injury. Neurotherapeutics 2012, 9: 405-421.
132. Wu J, Pajoohesh-Ganji A, Stoica BA, Dinizo M, Guanciale K, Faden A. Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion. J Neuroinflammation 2012, 9(1): 169.
133. Chen HC, Fong TH, Hsu PW, Chiu WT. Multifaceted effects of rapamycin on functional recovery after spinal cord injury in rats through autophagy promotion, anti-inflammation, and neuroprotection. J Surg Res 2012, 179(1): e203-210.
134. Su Z, Yuan Y, Cao L, Zhu Y, Gao L, Qiu Y, et al. Triptolide promotes spinal cord repair by inhibiting astrogliosis and inflammation. Glia 2010, 58(8): 901-915.
135. Nikulina E, Tidwell JL, Dai HN, Bregman BS, Filbin MT. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci U S A 2004, 101(23): 8786-8790.
136. Zhang S, Kluge B, Huang F, Nordstrom T, Doolen S, Gross M, et al. Photochemical scar ablation in chronically contused spinal cord of rat. J Neurotrauma 2007, 24(2): 411-420.
137. Pivat A, Gimenez-Ribotta M, Pencalet P, Kamenka JM. Experimental medullary lesions: prevention of the extension of secondary lesions and formation of glial scarring. Bull Acad Natl Med 1994, 178(3): 445-452; discussion 452-454.