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Targeting Inhibitory Chondroitin Sulphate Proteoglycans to Promote Plasticity After Injury

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Axon Growth and Regeneration

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1162))

Abstract

Chondroitin sulphate proteoglycans (CSPGs) are one of the major families of inhibitory extracellular matrix molecules in the central nervous system. The expression of various CSPGs is strong during early nervous system development; however, it is downregulated during maturation and up-regulated again after nervous system injury. In vivo injection of an enzyme called chondroitinase ABC, which removes the inhibitory chondroitin sulphate chains on the CSPGs, in the injured area promotes both the regeneration and plasticity of the neurons. Here, we describe the method of in vivo injection of the chondroitinase ABC into the cortex of adult rat brain and the histochemical method to assess the successfulness of the digestion.

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References

  1. Novak U, Kaye AH (2000) Extracellular matrix and the brain: components and function. J Clin Neurosci 7:280–290

    Article  CAS  PubMed  Google Scholar 

  2. Rhodes KE, Fawcett JW (2004) Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS? J Anat 204:33–48

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Yamaguchi Y (2000) Lecticans: organizers of the brain extracellular matrix. Cell Mol Life Sci 57:276–289

    Article  CAS  PubMed  Google Scholar 

  4. Kwok JC, Dick G, Wang D, Fawcett JW (2011) Extracellular matrix and perineuronal nets in CNS repair. Dev Neurobiol 71:1073–1089

    Article  CAS  PubMed  Google Scholar 

  5. Lemons ML, Howland DR, Anderson DK (1999) Chondroitin sulfate proteoglycan immunoreactivity increases following spinal cord injury and transplantation. Exp Neurol 160:51–65

    Article  CAS  PubMed  Google Scholar 

  6. Zuo J, Neubauer D, Dyess K, Ferguson TA, Muir D (1998) Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue. Exp Neurol 154:654–662

    Article  CAS  PubMed  Google Scholar 

  7. Bravin M, Savio T, Strata P, Rossi F (1997) Olivocerebellar axon regeneration and target reinnervation following dissociated Schwann cell grafts in surgically injured cerebella of adult rats. Eur J Neurosci 9: 2634–2649

    Article  CAS  PubMed  Google Scholar 

  8. Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME (2000) Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403: 434–439

    Article  CAS  PubMed  Google Scholar 

  9. Morrow DR, Campbell G, Lieberman AR, Anderson PN (1993) Differential regenerative growth of CNS axons into tibial and peroneal nerve grafts in the thalamus of adult rats. Exp Neurol 120:60–69

    Article  CAS  PubMed  Google Scholar 

  10. Kawaja MD, Gage FH (1991) Reactive astrocytes are substrates for the growth of adult CNS axons in the presence of elevated levels of nerve growth factor. Neuron 7:1019–1030

    Article  CAS  PubMed  Google Scholar 

  11. Smith GM, Jacobberger JW, Miller RH (1993) Modulation of adhesion molecule expression on rat cortical astrocytes during maturation. J Neurochem 60:1453–1466

    Article  CAS  PubMed  Google Scholar 

  12. 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

    Article  CAS  PubMed  Google Scholar 

  13. Yick LW, Wu W, So KF, Yip HK, Shum DK (2000) Chondroitinase ABC promotes axonal regeneration of Clarke’s neurons after spinal cord injury. Neuroreport 11:1063–1067

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  15. Galtrey CM, Asher RA, Nothias F, Fawcett JW (2007) Promoting plasticity in the spinal cord with chondroitinase improves functional recovery after peripheral nerve repair. Brain 130:926–939

    Article  PubMed  Google Scholar 

  16. Barritt AW, Davies M, Marchand F, Hartley R, Grist J, Yip P, McMahon SB, Bradbury EJ (2006) Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci 26: 10856–10867

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. 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

    Article  CAS  PubMed  Google Scholar 

  18. McRae PA, Rocco MM, Kelly G, Brumberg JC, Matthews RT (2006) Sensory deprivation alters aggrecan and perineuronal net expression in the mouse barrel cortex. J Neurosci 27:5405–5413

    Article  Google Scholar 

  19. Fawcett JW (2009) Recovery from spinal cord injury: regeneration, plasticity and rehabilitation. Brain 132:1417–1418

    Article  PubMed  Google Scholar 

  20. Fawcett JW, Curt A (2009) Damage control in the nervous system: rehabilitation in a plastic environment. Nat Med 15:735–736

    Article  CAS  PubMed  Google Scholar 

  21. Garcia-Alias G, Barkhuysen S, Buckle M, Fawcett JW (2009) Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci 12:1145–1151

    Article  CAS  PubMed  Google Scholar 

  22. Girgis J, Merrett D, Kirkland S, Metz GA, Verge V, Fouad K (2007) Reaching training in rats with spinal cord injury promotes plasticity and task specific recovery. Brain 130: 2993–3003

    Article  CAS  PubMed  Google Scholar 

  23. Tom VJ, Steinmetz MP, Miller JH, Doller CM, Silver J (2004) Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury. J Neurosci 24:6531–6539

    Article  CAS  PubMed  Google Scholar 

  24. Cafferty WB, Bradbury EJ, Lidierth M, Jones M, Duffy PJ, Pezet S, McMahon SB (2008) Chondroitinase ABC-mediated plasticity of spinal sensory function. J Neurosci 28: 11998–12009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Romberg C, Yang S, Melani R, Andrews MR, Horner AE, Spillantini MG, Bussey TJ, Fawcett JW, Pizzorusso T, Saksida LM (2013) Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex. J Neurosci 33: 7057–7065

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Gogolla N, Caroni P, Lüthi A, Herry C (2009) Perineuronal nets protect fear memories from erasure. Science 325:1258–1261

    Article  CAS  PubMed  Google Scholar 

  28. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic, San Diego

    Google Scholar 

  29. Cetin A, Komai S, Eliava M, Seeburg PH, Osten P (2007) Stereotaxic gene delivery in the rodent brain. Nat Protoc 1:3166–3173

    Article  Google Scholar 

  30. Lin R, Kwok JC, Crespo D, Fawcett JW (2008) Chondroitinase ABC has a long-lasting effect on chondroitin sulphate glycosaminoglycan content in the injured rat brain. J Neurochem 104:400–408

    CAS  PubMed  Google Scholar 

  31. Hyatt AJ, Wang D, Kwok JC, Fawcett JW, Martin KR (2010) Controlled release of chondroitinase ABC from fibrin gel reduces the level of inhibitory glycosaminoglycan chains in lesioned spinal cord. J Control Release 147: 24–29

    Article  CAS  PubMed  Google Scholar 

  32. Zhao RR, Muir EM, Alves JN, Rickman H, Allan AY, Kwok JC, Roet KC, Verhaagen J, Schneider BL, Bensadoun JC, Ahmed SG, Yáñez-Muñoz RJ, Keynes RJ, Fawcett JW, Rogers JH (2011) Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons. J Neurosci Methods 201:228–238

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Correspondence to Jessica C. F. Kwok .

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Kwok, J.C.F., Heller, J.P., Zhao, RR., Fawcett, J.W. (2014). Targeting Inhibitory Chondroitin Sulphate Proteoglycans to Promote Plasticity After Injury. In: Murray, A. (eds) Axon Growth and Regeneration. Methods in Molecular Biology, vol 1162. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0777-9_10

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  • DOI: https://doi.org/10.1007/978-1-4939-0777-9_10

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0776-2

  • Online ISBN: 978-1-4939-0777-9

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