Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier
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After spinal cord injury (SCI), re-establishing functional circuitry in the damaged central nervous system (CNS) faces multiple challenges including lost tissue volume, insufficient intrinsic growth capacity of adult neurons, and the inhibitory environment in the damaged CNS. Several treatment strategies have been developed over the past three decades, but successful restoration of sensory and motor functions will probably require a combination of approaches to address different aspects of the problem. Degradation of the chondroitin sulfate proteoglycans with the chondroitinase ABC (ChABC) enzyme removes a regeneration barrier from the glial scar and increases plasticity in the CNS by removing perineuronal nets. its mechanism of action does not clash or overlap with most of the other treatment strategies, making ChABC an attractive candidate as a combinational partner with other methods. in this article, we review studies in rat SCI models using ChABC combined with other treatments including cell implantation, growth factors, myelin-inhibitory molecule blockers, and ion channel expression. We discuss possible ways to optimize treatment protocols for future combinational studies. To date, combinational therapies with ChABC have shown synergistic effects with several other strategies in enhancing functional recovery after SCI. These combinatorial approaches can now be developed for clinical application.
- Hua R, Shi J, Wang X, Yang J, Zheng P, Cheng H, et al. Analysis of the causes and types of traumatic spinal cord injury based on 561 cases in China from 2001 to 2010. Spinal Cord 2013, 51: 218–221. CrossRef
- Lin R, Kwok JC, Crespo D, Fawcett JW. Chondroitinase ABC has a long-lasting effect on chondroitin sulphate glycosaminoglycan content in the injured rat brain. J Neurochem 2008, 104: 400–408. CrossRef
- Gilbert RJ, McKeon RJ, Darr A, Calabro A, Hascall VC, Bellamkonda RV. CS-4,6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension. Mol Cell Neurosci 2005, 29: 545–558. CrossRef
- Kwok JC, Carulli D, Fawcett JW. In vitro modeling of perineuronal nets: hyaluronan synthase and link protein are necessary for their formation and integrity. J Neurochem 2010, 114: 1447–1459.
- Kwok JC, Dick G, Wang D, Fawcett JW. Extracellular matrix and perineuronal nets in CNS repair. Dev Neurobiol 2011, 71: 1073–1089. CrossRef
- Galtrey CM, Kwok JC, Carulli D, Rhodes KE, Fawcett JW. Distribution and synthesis of extracellular matrix proteoglycans, hyaluronan, link proteins and tenascin-R in the rat spinal cord. Eur J Neurosci 2008, 27: 1373–1390. CrossRef
- Fawcett J. Molecular control of brain plasticity and repair. Prog Brain Res 2009, 175: 501–509. CrossRef
- Suzuki S, Saito H, Yamagata T, Anno K, Seno N, Kawai Y, et al. Formation of three types of disulfated disaccharides from chondroitin sulfates by chondroitinase digestion. J Biol Chem 1968, 243: 1543–1550.
- Crespo D, Asher RA, Lin R, Rhodes KE, JW F. How does chondroitinase promote functional recovery in the damaged CNS? Exp Neurol 2007, 206: 12. CrossRef
- Glant TT, Buzas EI, Finnegan A, Negroiu G, Cs-Szabo G, Mikecz K. Critical roles of glycosaminoglycan side chains of cartilage proteoglycan (aggrecan) in antigen recognition and presentation. J immunol 1998, 160: 3812–3819.
- Rolls A, Avidan H, Cahalon L, Schori H, Bakalash S, Litvak V, et al. A disaccharide derived from chondroitin sulphate proteoglycan promotes central nervous system repair in rats and mice. Eur J Neurosci 2004, 20: 1973–1983. CrossRef
- Garcia-Alias G, Barkhuysen S, Buckle M, Fawcett JW. Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci 2009, 12: 1145–1151. CrossRef
- 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: 636–640. CrossRef
- Garcia-Alias G, Lin R, Akrimi SF, Story D, Bradbury EJ, Fawcett JW. Therapeutic time window for the application of chondroitinase ABC after spinal cord injury. Exp Neurol 2008, 210: 331–338. CrossRef
- Moon LD, Asher RA, Rhodes KE, Fawcett JW. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nat Neurosci 2001, 4: 465–466.
- Wang D, Ichiyama RM, Zhao R, Andrews MR, Fawcett JW. Chondroitinase combined with rehabilitation promotes recovery of forelimb function in rats with chronic spinal cord injury. J Neurosci 2011, 31: 9332–9344. CrossRef
- Zuo J, Neubauer D, Dyess K, Ferguson TA, Muir D. Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue. Exp Neurol 1998, 154: 654–662. CrossRef
- Barritt AW, Davies M, Marchand F, Hartley R, Grist J, Yip P, et al. Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci 2006, 26: 10856–10867. CrossRef
- Kwok JC, Afshari F, Garcia-Alias G, Fawcett JW. Proteoglycans in the central nervous system: plasticity, regeneration and their stimulation with chondroitinase ABC. Restor Neurol Neurosci 2008, 26: 131–145.
- Zhao RR, Muir EM, Alves JN, Rickman H, Allan AY, Kwok JC, et al. Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons. J Neurosci Methods 2011, 201: 228–238. CrossRef
- Bunge MB. Novel combination strategies to repair the injured mammalian spinal cord. J Spinal Cord Med 2008, 31: 262–269.
- Grimpe B, Pressman Y, Lupa MD, Horn KP, Bunge MB, Silver J. The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces. Mol Cell Neurosci 2005, 28: 18–29. CrossRef
- Vavrek R, Pearse DD, Fouad K. Neuronal populations capable of regeneration following a combined treatment in rats with spinal cord transection. J Neurotrauma 2007, 24: 1667–1673. CrossRef
- Fouad K, Pearse DD, Tetzlaff W, Vavrek R. Transplantation and repair: combined cell implantation and chondroitinase delivery prevents deterioration of bladder function in rats with complete spinal cord injury. Spinal Cord 2009, 47: 727–732. CrossRef
- Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Schut D, Fehlings MG. Synergistic effects of transplanted adult neural stem/progenitor cells, chondroitinase, and growth factors promote functional repair and plasticity of the chronically injured spinal cord. J Neurosci 2010, 30: 1657–1676. CrossRef
- Hwang DH, Kim HM, Kang YM, Joo IS, Cho CS, Yoon BW, et al. Combination of multifaceted strategies to maximize the therapeutic benefits of neural stem cell transplant for spinal cord repair. Cell Transplant 2011, 20: 1361–1379. CrossRef
- Massey JM, Amps J, Viapiano MS, Matthews RT, Wagoner MR, Whitaker CM, et al. 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 2008, 209: 426–445. CrossRef
- Steinmetz MP, Horn KP, Tom VJ, Miller JH, Busch SA, Nair D, et al. Chronic enhancement of the intrinsic growth capacity of sensory neurons combined with the degradation of inhibitory proteoglycans allows functional regeneration of sensory axons through the dorsal root entry zone in the mammalian spinal cord. J Neurosci 2005, 25: 8066–8076. CrossRef
- Harel R, Iannotti CA, Hoh D, Clark M, Silver J, Steinmetz MP. Oncomodulin affords limited regeneration to injured sensory axons in vitro and in vivo. Exp Neurol 2012, 233: 708–716. CrossRef
- Bai F, Peng H, Etlinger JD, Zeman RJ. Partial functional recovery after complete spinal cord transection by combined chondroitinase and clenbuterol treatment. Pflugers Arch 2010, 460: 657–666. CrossRef
- Garcia-Alias G, Petrosyan HA, Schnell L, Horner PJ, Bowers WJ, Mendell LM, et al. Chondroitinase ABC combined with neurotrophin NT-3 secretion and NR2D expression promotes axonal plasticity and functional recovery in rats with lateral hemisection of the spinal cord. J Neurosci 2011, 31: 17788–17799. CrossRef
- Garcia-Alias G, Fawcett JW. Training and anti-CSPG combination therapy for spinal cord injury. Exp Neurol 2012, 235: 26–32. CrossRef
- Schwab ME. Nogo and axon regeneration. Curr opin Neurobiol 2004, 14: 118–124. CrossRef
- Yiu G, He Z. Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 2006, 7: 617–627. CrossRef
- Kopp MA, Liebscher T, Niedeggen A, Laufer S, Brommer B, Jungehulsing GJ, et al. Small-molecule-induced Rhoinhibition: NSAiDs after spinal cord injury. Cell Tissue Res 2012, 349: 119–132. CrossRef
- Oertle T, van der Haar ME, Bandtlow CE, Robeva A, Burfeind P, Buss A, et al. Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions. J Neurosci 2003, 23: 5393–5406.
- GrandPre T, Nakamura F, Vartanian T, Strittmatter SM. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 2000, 403: 439–444. CrossRef
- Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody iN-1. Nature 2000, 403: 434–439. CrossRef
- Zhao RR, Andrews MR, Wang D, Warren P, Gullo M, Schnell L, et al. Combination treatment with anti-Nogo-A and chondroitinase ABC is more effective than single treatments at enhancing functional recovery after spinal cord injury. Eur J Neurosci 2013. DOI: 10.1111/ejn.12276.
- Maier IC, Ichiyama RM, Courtine G, Schnell L, Lavrov I, Edgerton VR, et al. Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury. Brain 2009, 132: 1426–1440. CrossRef
- Marsh BC, Astill SL, Utley A, Ichiyama RM. Movement rehabilitation after spinal cord injuries: emerging concepts and future directions. Brain Res Bull 2011, 84: 327–336. CrossRef
- Courtine G, Roy RR, Hodgson J, McKay H, Raven J, Zhong H, et al. Kinematic and EMG determinants in quadrupedal locomotion of a non-human primate (Rhesus). J Neurophysiol 2005, 93: 3127–3145. CrossRef
- Ichiyama RM, Courtine G, Gerasimenko YP, Yang GJ, van den Brand R, Lavrov IA, et al. Step training reinforces specific spinal locomotor circuitry in adult spinal rats. J Neurosci 2008, 28: 7370–7375. CrossRef
- Galtrey CM, Fawcett JW. Characterization of tests of functional recovery after median and ulnar nerve injury and repair in the rat forelimb. J Peripher Nerv Syst 2007, 12: 11–27. CrossRef
- Montoya CP, Campbell-Hope LJ, Pemberton KD, Dunnett SB. The “staircase test”: a measure of independent forelimb reaching and grasping abilities in rats. J Neurosci Methods 1991, 36: 219–228. CrossRef
- Starkey ML, Barritt AW, Yip PK, Davies M, Hamers FP, McMahon SB, et al. Assessing behavioural function following a pyramidotomy lesion of the corticospinal tract in adult mice. Exp Neurol 2005, 195: 524–539. CrossRef
- Khaing ZZ, Geissler SA, Jiang S, Milman BD, Aguilar SV, Schmidt CE, et al. Assessing forelimb function after unilateral cervical spinal cord injury: novel forelimb tasks predict lesion severity and recovery. J Neurotrauma 2012, 29: 488–498. CrossRef
- Onifer SM, Rodriguez JF, Santiago DI, Benitez JC, Kim DT, Brunschwig JP, et al. Cervical spinal cord injury in the adult rat: assessment of forelimb dysfunction. Restor Neurol Neurosci 1997, 11: 211–223.
- Stackhouse SK, Murray M, Shumsky JS. Effect of cervical dorsolateral funiculotomy on reach-to-grasp function in the rat. J Neurotrauma 2008, 25: 1039–1047. CrossRef
- Metz GA, Whishaw IQ. The ladder rung walking task: a scoring system and its practical application. J Vis Exp 2009, (28). pii: 1204. doi: 10.3791/1204.
- Whishaw IQ, Travis SG, Koppe SW, Sacrey LA, Gholamrezaei G, Gorny B. Hand shaping in the rat: conserved release and collection vs. flexible manipulation in overground walking, ladder rung walking, cylinder exploration, and skilled reaching. Behav Brain Res 2010, 206: 21–31. CrossRef
- Gonzenbach RR, Gasser P, Zorner B, Hochreutener E, Dietz V, Schwab ME. Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats. Ann Neurol 2010, 68: 48–57. CrossRef
- Zorner B, Filli L, Starkey ML, Gonzenbach R, Kasper H, Rothlisberger M, et al. Profiling locomotor recovery: comprehensive quantification of impairments after CNS damage in rodents. Nat Methods 2010, 7: 701–708. CrossRef
- Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier
Volume 29, Issue 4 , pp 477-483
- Cover Date
- Print ISSN
- Online ISSN
- Springer Berlin Heidelberg
- Additional Links
- spinal cord injury
- combination treatment
- chondroitinase ABC
- chondroitin sulfate proteoglycan
- axon regeneration