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The laser lesion of the mouse visual cortex as a model to study neural extracellular matrix remodeling during degeneration, regeneration and plasticity of the CNS


CNS lesions generally result in impaired function because regeneration of the adult CNS of mammals is poor. A variety of lesion models has been described that serve to further the understanding of the pathophysiology of the damaged tissue. A central cause of aborted regeneration is the glial scar that expresses a plethora of extracellular matrix molecules. Some of these are considered inhibitors of axon growth and regeneration. The laser lesion of the cortex offers the advantage that a circumscribed lesion of defined energy can be delivered to the cortex non-invasively through the intact dura mater and a thinly drilled wet translucent remnant of the skull. Previously, we have shown that distinct ECM is up-regulated in the penumbra of laser lesions in the rat visual cortex. We propose to transfer this model to the mouse, in view of the availability of a large number of genetical models in this small rodent. Here, we discuss this model and the lesion-related ECM that forms the focus of our analysis.

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  1. Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, Small JE, Herrlinger U, Ourednik V, Black PM, Breakefield XO, Snyder EY (2000) Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci USA 97:12846–12851

  2. Adachi K, Mirzadeh Z, Sakaguchi M, Yamashita T, Nikolcheva T, Gotoh Y, Peltz G, Gong L, Kawase T, Alvarez-Buylla A, Okano H, Sawamoto K (2007) Beta-catenin signaling promotes proliferation of progenitor cells in the adult mouse subventricular zone. Stem Cells 25:2827–2836

  3. Akita K, von Holst A, Furukawa Y, Mikami T, Sugahara K, Faissner A (2008) 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

  4. Alvarez-Buylla A, Lim DA (2004) For the long run: maintaining germinal niches in the adult brain. Neuron 41:683–686

  5. Angot E, Loulier K, Nguyen-Ba-Charvet KT, Gadeau AP, Ruat M, Traiffort E (2008) Chemoattractive activity of sonic hedgehog in the adult subventricular zone modulates the number of neural precursors reaching the olfactory bulb. Stem Cells 26:2311–2320

  6. Anthony TE, Klein C, Fishell G, Heintz N (2004) Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron 41:881–890

  7. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8:963–970

  8. Balordi F, Fishell G (2007) Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons. J Neurosci 27:5936–5947

  9. Bandtlow CE, Zimmermann DR (2000) Proteoglycans in the developing brain: new conceptual insights for old proteins. Physiol Rev 80:1267–1290

  10. Bao X, Mikami T, Yamada S, Faissner A, Muramatsu T, Sugahara K (2005) Heparin-binding growth factor, pleiotrophin, mediates neuritogenic activity of embryonic pig brain-derived chondroitin sulfate/dermatan sulfate hybrid chains. J Biol Chem 280:9180–9191

  11. Barmashenko G, Eysel UT, Mittmann T (2003) Changes in intracellular calcium transients and LTP in the surround of visual cortex lesions in rats. Brain Res 990:120–128

  12. Bartsch S, Bartsch U, Dorries U, Faissner A, Weller A, Ekblom P, Schachner M (1992) Expression of tenascin in the developing and adult cerebellar cortex. J Neurosci 12:736–749

  13. Bath KG, Akins MR, Lee FS (2011) BDNF control of adult SVZ neurogenesis. Dev Psychobiol (in press)

  14. 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

  15. Brodkey JA, Laywell ED, O'Brien TF, Faissner A, Stefansson K, Dorries HU, Schachner M, Steindler DA (1995) Focal brain injury and upregulation of a developmentally regulated extracellular matrix protein. J Neurosurg 82:106–112

  16. Busch SA, Silver J (2007) The role of extracellular matrix in CNS regeneration. Curr Opin Neurobiol 17:120–127

  17. Bystron I, Blakemore C, Rakic P (2008) Development of the human cerebral cortex: Boulder Committee revisited. Nat Rev Neurosci 9:110–122

  18. Carulli D, Laabs T, Geller HM, Fawcett JW (2005) Chondroitin sulfate proteoglycans in neural development and regeneration. Curr Opin Neurobiol 15:116–120

  19. Chen J, Joon Lee H, Jakovcevski I, Shah R, Bhagat N, Loers G, Liu HY, Meiners S, Taschenberger G, Kugler S, Irintchev A, Schachner M (2010) The extracellular matrix glycoprotein tenascin-C is beneficial for spinal cord regeneration. Mol Ther 18:1769–1777

  20. Chiquet-Ehrismann R, Chiquet M (2003) Tenascins: regulation and putative functions during pathological stress. J Pathol 200:488–499

  21. Chiquet-Ehrismann R, Tucker RP (2011) Tenascins and the importance of adhesion modulation. Cold Spring Harb Perspect Biol 3:

  22. Chow JP, Fujikawa A, Shimizu H, Suzuki R, Noda M (2008) Metalloproteinase- and gamma-secretase-mediated cleavage of protein-tyrosine phosphatase receptor type Z. J Biol Chem 283:30879–30889

  23. Clement AM, Nadanaka S, Masayama K, Mandl C, Sugahara K, Faissner A (1998) The DSD-1 carbohydrate epitope depends on sulfation, correlates with chondroitin sulfate D motifs, and is sufficient to promote neurite outgrowth. J Biol Chem 273:28444–28453

  24. Czopka T, von Holst A, ffrench-Constant C, Faissner A (2010) Regulatory mechanisms that mediate tenascin C-dependent inhibition of oligodendrocyte precursor differentiation. J Neurosci 30:12310–12322

  25. Czopka T, Von Holst A, Schmidt G, Ffrench-Constant C, Faissner A (2009) Tenascin C and tenascin R similarly prevent the formation of myelin membranes in a RhoA-dependent manner, but antagonistically regulate the expression of myelin basic protein via a separate pathway. Glia 57:1790–1801

  26. Deller T, Haas CA, Naumann T, Joester A, Faissner A, Frotscher M (1997) Up-regulation of astrocyte-derived tenascin-C correlates with neurite outgrowth in the rat dentate gyrus after unilateral entorhinal cortex lesion. Neuroscience 81:829–846

  27. Dobbertin A, Czvitkovich S, Theocharidis U, Garwood J, Andrews MR, Properzi F, Lin R, Fawcett JW, Faissner A (2010) Analysis of combinatorial variability reveals selective accumulation of the fibronectin type III domains B and D of tenascin-C in injured brain. Exp Neurol 225:60–73

  28. Dobbertin A, Rhodes KE, Garwood J, Properzi F, Heck N, Rogers JH, Fawcett JW, Faissner A (2003) Regulation of RPTPbeta/phosphacan expression and glycosaminoglycan epitopes in injured brain and cytokine-treated glia. Mol Cell Neurosci 24:951–971

  29. Dohle CI, Eysel UT, Mittmann T (2009) Spatial distribution of long-term potentiation in the surround of visual cortex lesions in vitro. Exp Brain Res 199:423–433

  30. Eysel UT, Schweigart G (1999) Increased receptive field size in the surround of chronic lesions in the adult cat visual cortex. Cereb Cortex 9:101–109

  31. Eysel UT, Schweigart G, Mittmann T, Eyding D, Qu Y, Vandesande F, Orban G, Arckens L (1999) Reorganization in the visual cortex after retinal and cortical damage. Restor Neurol Neurosci 15:153–164

  32. Faissner A (1997a) Glial Derived Extracellular matrix Components: Important Roles in Axon Growth and Guidance. Neuroscientist 3:371–380

  33. Faissner A (1997b) The tenascin gene family in axon growth and guidance. Cell Tissue Res 290:331–341

  34. Faissner A, Clement A, Lochter A, Streit A, Mandl C, Schachner M (1994a) Isolation of a neural chondroitin sulfate proteoglycan with neurite outgrowth promoting properties. J Cell Biol 126:783–799

  35. Faissner A, Heck N, Dobbertin A, Garwood J (2006) DSD-1-Proteoglycan/Phosphacan and receptor protein tyrosine phosphatase-beta isoforms during development and regeneration of neural tissues. Adv Exp Med Biol 557:25–53

  36. Faissner A, Kruse J (1990) J1/tenascin is a repulsive substrate for central nervous system neurons. Neuron 5:627–637

  37. Faissner A, Pyka M, Geissler M, Sobik T, Frischknecht R, Gundelfinger ED, Seidenbecher C (2010) Contributions of astrocytes to synapse formation and maturation - Potential functions of the perisynaptic extracellular matrix. Brain Res Rev 63:26–38

  38. Faissner A, Scholze A, Götz B (1994b) Tenascin glycoproteins in developing neural tissues: only decoration? Perspect Dev Neurobiol 2:53–66

  39. Faissner A, Steindler D (1995) Boundaries and inhibitory molecules in developing neural tissues. Glia 13:233–254

  40. Fawcett J (2009) Molecular control of brain plasticity and repair. Prog Brain Res 175:501–509

  41. Fawcett JW (2006a) The glial response to injury and its role in the inhibition of CNS repair. Adv Exp Med Biol 557:11–24

  42. Fawcett JW (2006b) Overcoming inhibition in the damaged spinal cord. J Neurotrauma 23:371–383

  43. Fitch MT, Silver J (2008) CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp Neurol 209:294–301

  44. Flanders KC, Ren RF, Lippa CF (1998) Transforming growth factor-betas in neurodegenerative disease. Prog Neurobiol 54:71–85

  45. Galtrey CM, Kwok JC, Carulli D, Rhodes KE, Fawcett JW (2008) Distribution and synthesis of extracellular matrix proteoglycans, hyaluronan, link proteins and tenascin-R in the rat spinal cord. Eur J Neurosci 27:1373–1390

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

  47. Garcion E, Halilagic A, Faissner A, ffrench-Constant C (2004) Generation of an environmental niche for neural stem cell development by the extracellular matrix molecule tenascin C. Development 131:3423–3432

  48. Garwood J, Garcion E, Dobbertin A, Heck N, Calco V, ffrench-Constant C, Faissner A (2004) 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

  49. Garwood J, Heck N, Reichardt F, Faissner A (2003) Phosphacan short isoform, a novel non-proteoglycan variant of phosphacan/receptor protein tyrosine phosphatase-beta, interacts with neuronal receptors and promotes neurite outgrowth. J Biol Chem 278:24164–24173

  50. Garwood J, Rigato F, Heck N, Faissner A (2001) Tenascin glycoproteins and the complementary ligand DSD-1-PG/ phosphacan–structuring the neural extracellular matrix during development and repair. Restor Neurol Neurosci 19:51–64

  51. Garwood J, Schnadelbach O, Clement A, Schutte K, Bach A, Faissner A (1999) DSD-1-proteoglycan is the mouse homolog of phosphacan and displays opposing effects on neurite outgrowth dependent on neuronal lineage. J Neurosci 19:3888–3899

  52. Garzon-Muvdi T, Quinones-Hinojosa A (2009) Neural stem cell niches and homing: recruitment and integration into functional tissues. ILAR J 51:3–23

  53. Gates MA, Thomas LB, Howard EM, Laywell ED, Sajin B, Faissner A, Götz B, Silver J, Steindler DA (1995) Cell and molecular analysis of the developing and adult mouse subventricular zone of the cerebral hemispheres. J Comp Neurol 361:249–266

  54. Götz B, Scholze A, Clement A, Joester A, Schutte K, Wigger F, Frank R, Spiess E, Ekblom P, Faissner A (1996) Tenascin-C contains distinct adhesive, anti-adhesive, and neurite outgrowth promoting sites for neurons. J Cell Biol 132:681–699

  55. Götz M, Bolz J, Joester A, Faissner A (1997) Tenascin-C synthesis and influence on axonal growth during rat cortical development. Eur J Neurosci 9:496–506

  56. Götz M, Huttner WB (2005) The cell biology of neurogenesis. Nat Rev Mol Cell Biol 6:777–788

  57. Hartfuss E, Galli R, Heins N, Götz M (2001) Characterization of CNS precursor subtypes and radial glia. Dev Biol 229:15–30

  58. Heck N, Garwood J, Dobbertin A, Calco V, Sirko S, Mittmann T, Eysel UT, Faissner A (2007) Evidence for distinct leptomeningeal cell-dependent paracrine and EGF-linked autocrine regulatory pathways for suppression of fibrillar collagens in astrocytes. Mol Cell Neurosci 36:71–85

  59. Heck N, Garwood J, Schutte K, Fawcett J, Faissner A (2003) Astrocytes in culture express fibrillar collagen. Glia 41:382–392

  60. Heins N, Malatesta P, Cecconi F, Nakafuku M, Tucker KL, Hack MA, Chapouton P, Barde YA, Götz M (2002) Glial cells generate neurons: the role of the transcription factor Pax6. Nat Neurosci 5:308–315

  61. Hennen E, Czopka T, Faissner A (2011) Structurally Distinct LewisX Glycans Distinguish Subpopulations of Neural Stem/Progenitor Cells. J Biol Chem 286:16321–16331

  62. Hikino M, Mikami T, Faissner A, Vilela-Silva AC, Pavao MS, Sugahara K (2003) 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

  63. Huemmeke M, Eysel UT, Mittmann T (2004) Lesion-induced enhancement of LTP in rat visual cortex is mediated by NMDA receptors containing the NR2B subunit. J Physiol 559:875–882

  64. Husmann K, Faissner A, Schachner M (1992) Tenascin promotes cerebellar granule cell migration and neurite outgrowth by different domains in the fibronectin type III repeats. J Cell Biol 116:1475–1486

  65. Ida M, Shuo T, Hirano K, Tokita Y, Nakanishi K, Matsui F, Aono S, Fujita H, Fujiwara Y, Kaji T, Oohira A (2006) Identification and functions of chondroitin sulfate in the milieu of neural stem cells. J Biol Chem 281:5982–5991

  66. Ihrie RA, Alvarez-Buylla A (2011) Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain. Neuron 70:674–686

  67. Imayoshi I, Sakamoto M, Ohtsuka T, Takao K, Miyakawa T, Yamaguchi M, Mori K, Ikeda T, Itohara S, Kageyama R (2008) Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci 11:1153–1161

  68. Imbrosci B, Eysel UT, Mittmann T (2010) Metaplasticity of horizontal connections in the vicinity of focal laser lesions in rat visual cortex. J Physiol 588:4695–4703

  69. Ito Y, Hikino M, Yajima Y, Mikami T, Sirko S, von Holst A, Faissner A, Fukui S, Sugahara K (2005) Structural characterization of the epitopes of the monoclonal antibodies 473HD, CS-56, and MO-225 specific for chondroitin sulfate D-type using the oligosaccharide library. Glycobiology 15:593–603

  70. Jallo GI, Kothbauer KF, Epstein FJ (2002) Contact laser microsurgery. Childs Nerv Syst 18:333–336

  71. Joester A, Faissner A (1999) Evidence for combinatorial variability of tenascin-C isoforms and developmental regulation in the mouse central nervous system. J Biol Chem 274:17144–17151

  72. Joester A, Faissner A (2001) The structure and function of tenascins in the nervous system. Matrix Biol 20:13–22

  73. Jones FS, Jones PL (2000) The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling. Dev Dyn 218:235–259

  74. Kabos P, Matundan H, Zandian M, Bertolotto C, Robinson ML, Davy BE, Yu JS, Krueger RC Jr (2004) Neural precursors express multiple chondroitin sulfate proteoglycans, including the lectican family. Biochem Biophys Res Commun 318:955–963

  75. Karus M, Denecke B, Ffrench-Constant C, Wiese S, Faissner A (2011) The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification. Development 138:5321–5331

  76. Kazanis I (2009) The subependymal zone neurogenic niche: a beating heart in the centre of the brain: how plastic is adult neurogenesis? Opportunities for therapy and questions to be addressed. Brain 132:2909–2921

  77. Kazanis I, Ffrench-Constant C (2011) Extracellular matrix and the neural stem cell niche. Dev Neurobiol 71:1006–1017

  78. Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27:447–452

  79. Kokovay E, Goderie S, Wang Y, Lotz S, Lin G, Sun Y, Roysam B, Shen Q, Temple S (2010) Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. Cell Stem Cell 7:163–173

  80. Kriegstein A, Alvarez-Buylla A (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32:149–184

  81. Kronenberg G, Reuter K, Steiner B, Brandt MD, Jessberger S, Yamaguchi M, Kempermann G (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–463

  82. Kwok JC, Afshari F, Garcia-Alias G, Fawcett JW (2008) Proteoglycans in the central nervous system: plasticity, regeneration and their stimulation with chondroitinase ABC. Restor Neurol Neurosci 26:131–145

  83. Laywell ED, Dorries U, Bartsch U, Faissner A, Schachner M, Steindler DA (1992) Enhanced expression of the developmentally regulated extracellular matrix molecule tenascin following adult brain injury. Proc Natl Acad Sci USA 89:2634–2638

  84. Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28:713–726

  85. Lochter A, Vaughan L, Kaplony A, Prochiantz A, Schachner M, Faissner A (1991) J1/tenascin in substrate-bound and soluble form displays contrary effects on neurite outgrowth. J Cell Biol 113:1159–1171

  86. Mahler M, Ben-Ari Y, Represa A (1997) Differential expression of fibronectin, tenascin-C and NCAMs in cultured hippocampal astrocytes activated by kainate, bacterial lipopolysaccharide or basic fibroblast growth factor. Brain Res 775:63–73

  87. Malatesta P, Hack MA, Hartfuss E, Kettenmann H, Klinkert W, Kirchhoff F, Götz M (2003) Neuronal or glial progeny: regional differences in radial glia fate. Neuron 37:751–764

  88. Malatesta P, Hartfuss E, Götz M (2000) Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127:5253–5263

  89. Massey JM, Amps J, Viapiano MS, Matthews RT, Wagoner MR, Whitaker CM, Alilain W, Yonkof AL, Khalyfa A, Cooper NG, Silver J, Onifer SM (2008) Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3. Exp Neurol 209:426–445

  90. 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

  91. Meiners S, Geller HM (1997) Long and short splice variants of human tenascin differentially regulate neurite outgrowth. Mol Cell Neurosci 10:100–116

  92. Meiners S, Marone M, Rittenhouse JL, Geller HM (1993) Regulation of astrocytic tenascin by basic fibroblast growth factor. Dev Biol 160:480–493

  93. Meiners S, Mercado ML, Nur-e-Kamal MS, Geller HM (1999a) Tenascin-C contains domains that independently regulate neurite outgrowth and neurite guidance. J Neurosci 19:8443–8453

  94. Meiners S, Nur-e-Kamal MS, Mercado ML (2001) Identification of a neurite outgrowth-promoting motif within the alternatively spliced region of human tenascin-C. J Neurosci 21:7215–7225

  95. Meiners S, Powell EM, Geller HM (1999b) Neurite outgrowth promotion by the alternatively spliced region of tenascin-C is influenced by cell-type specific binding. Matrix Biol 18:75–87

  96. Mercado ML, Nur-e-Kamal A, Liu HY, Gross SR, Movahed R, Meiners S (2004) Neurite outgrowth by the alternatively spliced region of human tenascin-C is mediated by neuronal alpha7beta1 integrin. J Neurosci 24:238–247

  97. Mercier F, Kitasako JT, Hatton GI (2002) Anatomy of the brain neurogenic zones revisited: fractones and the fibroblast/macrophage network. J Comp Neurol 451:170–188

  98. Merkle FT, Alvarez-Buylla A (2006) Neural stem cells in mammalian development. Curr Opin Cell Biol 18:704–709

  99. Merkle FT, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A (2004) Radial glia give rise to adult neural stem cells in the subventricular zone. Proc Natl Acad Sci USA 101:17528–17532

  100. Michele M, Faissner A (2009) Tenascin-C stimulates contactin-dependent neurite outgrowth via activation of phospholipase C. Mol Cell Neurosci 41:397–408

  101. Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A (2008) Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3:265–278

  102. Mittmann T, Eysel UT (2001) Increased synaptic plasticity in the surround of visual cortex lesions in rats. Neuroreport 12:3341–3347

  103. Miyata T, Kawaguchi A, Okano H, Ogawa M (2001) Asymmetric inheritance of radial glial fibers by cortical neurons. Neuron 31:727–741

  104. Mohyeldin A, Garzon-Muvdi T, Quinones-Hinojosa A (2010) Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell 7:150–161

  105. Moritz S, Lehmann S, Faissner A, von Holst A (2008) An induction gene trap screen in neural stem cells reveals an instructive function of the niche and identifies the splicing regulator sam68 as a tenascin-C-regulated target gene. Stem Cells 26:2321–2331

  106. Nadanaka S, Clement A, Masayama K, Faissner A, Sugahara K (1998) Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with a neurite outgrowth promoting activity. J Biol Chem 273:3296–3307

  107. Nakatomi H, Kuriu T, Okabe S, Yamamoto S, Hatano O, Kawahara N, Tamura A, Kirino T, Nakafuku M (2002) Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 110:429–441

  108. Nakic M, Mitrovic N, Sperk G, Schachner M (1996) Kainic acid activates transient expression of tenascin-C in the adult rat hippocampus. J Neurosci Res 44:355–362

  109. Niquet J, Jorquera I, Faissner A, Ben-Ari Y, Represa A (1995) Gliosis and axonal sprouting in the hippocampus of epileptic rats are associated with an increase of tenascin-C immunoreactivity. J Neurocytol 24:611–624

  110. Noctor SC, Flint AC, Weissman TA, Dammerman RS, Kriegstein AR (2001) Neurons derived from radial glial cells establish radial units in neocortex. Nature 409:714–720

  111. Noctor SC, Flint AC, Weissman TA, Wong WS, Clinton BK, Kriegstein AR (2002) Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia. J Neurosci 22:3161–3173

  112. Palma V, Lim DA, Dahmane N, Sanchez P, Brionne TC, Herzberg CD, Gitton Y, Carleton A, Alvarez-Buylla A, Ruiz i Altaba A (2005) Sonic hedgehog controls stem cell behavior in the postnatal and adult brain. Development 132:335–344

  113. Peretto P, Cummings D, Modena C, Behrens M, Venkatraman G, Fasolo A, Margolis FL (2002) BMP mRNA and protein expression in the developing mouse olfactory system. J Comp Neurol 451:267–278

  114. Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L (2002) Reactivation of ocular dominance plasticity in the adult visual cortex. Science 298:1248–1251

  115. Platel JC, Stamboulian S, Nguyen I, Bordey A (2010) Neurotransmitter signaling in postnatal neurogenesis: The first leg. Brain Res Rev 63:60–71

  116. Prieto AL, Jones FS, Cunningham BA, Crossin KL, Edelman GM (1990) Localization during development of alternatively spliced forms of cytotactin mRNA by in situ hybridization. J Cell Biol 111:685–698

  117. Properzi F, Carulli D, Asher RA, Muir E, Camargo LM, van Kuppevelt TH, ten Dam GB, Furukawa Y, Mikami T, Sugahara K, Toida T, Geller HM, Fawcett JW (2005) Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia. Eur J Neurosci 21:378–390

  118. Rauch U, Clement A, Retzler C, Frohlich L, Fassler R, Gohring W, Faissner A (1997) Mapping of a defined neurocan binding site to distinct domains of tenascin-C. J Biol Chem 272:26905–26912

  119. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710

  120. Richardson RM, Sun D, Bullock MR (2007) Neurogenesis after traumatic brain injury. Neurosurg Clin N Am 18:169-181, xi

  121. Rigato F, Garwood J, Calco V, Heck N, Faivre-Sarrailh C, Faissner A (2002) Tenascin-C promotes neurite outgrowth of embryonic hippocampal neurons through the alternatively spliced fibronectin type III BD domains via activation of the cell adhesion molecule F3/contactin. J Neurosci 22:6596–6609

  122. Robel S, Berninger B, Götz M (2011) The stem cell potential of glia: lessons from reactive gliosis. Nat Rev Neurosci 12:88–104

  123. Rumpel S, Hoffmann H, Hatt H, Gottmann K, Mittmann T, Eysel UT (2000) Lesion-induced changes in NMDA receptor subunit mRNA expression in rat visual cortex. Neuroreport 11:4021–4025

  124. Scadden DT (2006) The stem-cell niche as an entity of action. Nature 441:1075–1079

  125. Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, Abramova N, Vincent P, Pumiglia K, Temple S (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304:1338–1340

  126. Shen Q, Wang Y, Kokovay E, Lin G, Chuang SM, Goderie SK, Roysam B, Temple S (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 3:289–300

  127. Siddiqui S, Horvat-Bröcker A, Faissner A (2008) The glia-derived extracellular matrix glycoprotein tenascin-C promotes embryonic and postnatal retina axon outgrowth via the alternatively spliced fibronectin type III domain TNfnD. Neuron Glia Biol 4:271–283

  128. Siddiqui S, Horvat-Bröcker A, Faissner A (2009) Comparative screening of glial cell types reveals extracellular matrix that inhibits retinal axon growth in a chondroitinase ABC-resistant fashion. Glia 57:1420–1438

  129. Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146–156

  130. Singla V, Reiter JF (2006) The primary cilium as the cell's antenna: signaling at a sensory organelle. Science 313:629–633

  131. Sirko S, Akita K, Von Holst A, Faissner A (2010a) Structural and functional analysis of chondroitin sulfate proteoglycans in the neural stem cell niche. Methods Enzymol 479:37–71

  132. Sirko S, Neitz A, Mittmann T, Horvat-Bröcker A, von Holst A, Eysel UT, Faissner A (2009) Focal laser-lesions activate an endogenous population of neural stem/progenitor cells in the adult visual cortex. Brain 132:2252–2264

  133. Sirko S, von Holst A, Weber A, Wizenmann A, Theocharidis U, Götz M, Faissner A (2010b) Chondroitin sulfates are required for fibroblast growth factor-2-dependent proliferation and maintenance in neural stem cells and for epidermal growth factor-dependent migration of their progeny. Stem Cells 28:775–787

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

  135. Smith-Thomas LC, Fok-Seang J, Stevens J, Du JS, Muir E, Faissner A, Geller HM, Rogers JH, Fawcett JW (1994) An inhibitor of neurite outgrowth produced by astrocytes. J Cell Sci 107:1687–1695

  136. Smith-Thomas LC, Stevens J, Fok-Seang J, Faissner A, Rogers JH, Fawcett JW (1995) Increased axon regeneration in astrocytes grown in the presence of proteoglycan synthesis inhibitors. J Cell Sci 108:1307–1315

  137. Smith C, Berry M, Clarke WE, Logan A (2001) Differential expression of fibroblast growth factor-2 and fibroblast growth factor receptor 1 in a scarring and nonscarring model of CNS injury in the rat. Eur J Neurosci 13:443–456

  138. Smith GM, Hale JH (1997) Macrophage/Microglia regulation of astrocytic tenascin: synergistic action of transforming growth factor-beta and basic fibroblast growth factor. J Neurosci 17:9624–9633

  139. Tang X, Davies JE, Davies SJ (2003) 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

  140. Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, Garcia-Verdugo JM, Doetsch F (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3:279–288

  141. Taylor J, Pesheva P, Schachner M (1993) Influence of janusin and tenascin on growth cone behavior in vitro. J Neurosci Res 35:347–362

  142. Temple S (2001) The development of neural stem cells. Nature 414:112–117

  143. Thored P, Arvidsson A, Cacci E, Ahlenius H, Kallur T, Darsalia V, Ekdahl CT, Kokaia Z, Lindvall O (2006) Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24:739–747

  144. Treloar HB, Ray A, Dinglasan LA, Schachner M, Greer CA (2009) Tenascin-C is an inhibitory boundary molecule in the developing olfactory bulb. J Neurosci 29:9405–9416

  145. Tucker RP, Drabikowski K, Hess JF, Ferralli J, Chiquet-Ehrismann R, Adams JC (2006) Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage. BMC Evol Biol 6:60

  146. Ueoka C, Kaneda N, Okazaki I, Nadanaka S, Muramatsu T, Sugahara K (2000) Neuronal cell adhesion, mediated by the heparin-binding neuroregulatory factor midkine, is specifically inhibited by chondroitin sulfate E. Structural ans functional implications of the over-sulfated chondroitin sulfate. J Biol Chem 275:37407–37413

  147. Verma P, Garcia-Alias G, Fawcett JW (2008) Spinal cord repair: bridging the divide. Neurorehabil Neural Repair 22:429–437

  148. von Holst A, Egbers U, Prochiantz A, Faissner A (2007) Neural stem/progenitor cells express 20 tenascin C isoforms that are differentially regulated by Pax6. J Biol Chem 282:9172–9181

  149. von Holst A, Sirko S, Faissner A (2006) The unique 473HD-Chondroitinsulfate epitope is expressed by radial glia and involved in neural precursor cell proliferation. J Neurosci 26:4082–4094

  150. Wodarz A, Huttner WB (2003) Asymmetric cell division during neurogenesis in Drosophila and vertebrates. Mech Dev 120:1297–1309

  151. Yu YM, Cristofanilli M, Valiveti A, Ma L, Yoo M, Morellini F, Schachner M (2011) The extracellular matrix glycoprotein tenascin-C promotes locomotor recovery after spinal cord injury in adult zebrafish. Neuroscience 183:238–250

  152. 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

  153. Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660

  154. Zou P, Zou K, Muramatsu H, Ichihara-Tanaka K, Habuchi O, Ohtake S, Ikematsu S, Sakuma S, Muramatsu T (2003) Glycosaminoglycan structures required for strong binding to midkine, a heparin-binding growth factor. Glycobiology 13:35–42

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We gratefully acknowledge grant support by the German Research Foundation (DFG, SFB 509, SPP-1172, GRK-736), the Federal Ministry of Education and Research (BMBF), the Land NRW (Stem Cell Network NRW, International Graduate School of Neuroscience IGSN), the Ruhr-University Bochum (Rectorate programs) and the Mercator Foundation.

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Correspondence to Andreas Faissner.

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Roll, L., Mittmann, T., Eysel, U.T. et al. The laser lesion of the mouse visual cortex as a model to study neural extracellular matrix remodeling during degeneration, regeneration and plasticity of the CNS. Cell Tissue Res 349, 133–145 (2012). https://doi.org/10.1007/s00441-011-1313-4

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  • Neural stem cells
  • Tenascin
  • Phosphacan/DSD-1-PG
  • Chondroitin sulfate proteoglycans
  • Stem cell niche