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Combination treatment with anti-Nogo-A and chondroitinase ABC is more effective than single treatments at enhancing functional recovery after spinal cord injury

Combination treatment with anti-Nogo-A and chondroitinase ABC is more effective than single treatments at enhancing functional recovery after spinal cord injury
Combination treatment with anti-Nogo-A and chondroitinase ABC is more effective than single treatments at enhancing functional recovery after spinal cord injury

Anti-Nogo-A antibody and chondroitinase ABC (ChABC) enzyme are two promising treatments that promote functional recovery after spinal cord injury (SCI). Treatment with them has encouraged axon regeneration, sprouting and functional recovery in a variety of spinal cord and central nervous system injury models. The two compounds work, in part, through different mechanisms, so it is possible that their effects will be additive. In this study, we used a rat cervical partial SCI model to explore the effectiveness of a combination of anti-Nogo-A, ChABC, and rehabilitation. We found that spontaneous recovery of forelimb functions reflects the extent of the lesion on the ipsilateral side. We applied a combination treatment with acutely applied anti-Nogo-A antibody followed by delayed ChABC treatment starting at 3 weeks after injury, and rehabilitation starting at 4 weeks, to accommodate the requirement that anti-Nogo-A be applied acutely, and that rehabilitation be given after the cessation of anti-Nogo-A treatment. We found that single treatment with either anti-Nogo-A or ChABC, combined with rehabilitation, produced functional recovery of similar magnitude. The combination treatment, however, was more effective. Both single treatments produced increases in sprouting and axon regeneration, but the combination treatment produced greater increases. Anti-Nogo-A stimulated growth of a greater number of axons with a diameter of > 3 μm, whereas ChABC treatment stimulated increased growth of finer axons with varicosities. These results point to different functions of Nogo-A and chondroitin sulfate proteoglycans in axonal regeneration. The combination of anti-Nogo-A, ChABC and rehabilitation shows promise for enhancing functional recovery after SCI.

axon regeneration, chondroitinase, Nogo-A, plasticity, rehabilitation, spinal cord
0953-816X
2946-61
Zhao, Rong-Rong
a01f4196-18a6-4ad5-ac3d-aff1d528d88a
Andrews, Melissa R.
ae987a2f-878e-4ae3-a7a3-a7170712096c
Wang, Difei
9715478c-bba1-4418-ae99-1694f4bbfa08
Warren, Philippa
99d46b7e-d8d4-402b-942e-79685dbc1908
Gullo, Miriam
42e24982-f35f-47ae-b541-a6325cec0542
Schnell, Lisa
771a924d-f840-4796-be2f-da9a1ca0f65a
Schwab, Martin E.
36a9e39c-250a-4908-849d-c6675d5ec700
Fawcett, James W.
4549730e-9f62-45b8-820b-8a9c98d1058b
Zhao, Rong-Rong
a01f4196-18a6-4ad5-ac3d-aff1d528d88a
Andrews, Melissa R.
ae987a2f-878e-4ae3-a7a3-a7170712096c
Wang, Difei
9715478c-bba1-4418-ae99-1694f4bbfa08
Warren, Philippa
99d46b7e-d8d4-402b-942e-79685dbc1908
Gullo, Miriam
42e24982-f35f-47ae-b541-a6325cec0542
Schnell, Lisa
771a924d-f840-4796-be2f-da9a1ca0f65a
Schwab, Martin E.
36a9e39c-250a-4908-849d-c6675d5ec700
Fawcett, James W.
4549730e-9f62-45b8-820b-8a9c98d1058b

Zhao, Rong-Rong, Andrews, Melissa R., Wang, Difei, Warren, Philippa, Gullo, Miriam, Schnell, Lisa, Schwab, Martin E. and Fawcett, James W. (2013) Combination treatment with anti-Nogo-A and chondroitinase ABC is more effective than single treatments at enhancing functional recovery after spinal cord injury. European Journal of Neuroscience, 38 (6), 2946-61. (doi:10.1111/ejn.12276).

Record type: Article

Abstract

Anti-Nogo-A antibody and chondroitinase ABC (ChABC) enzyme are two promising treatments that promote functional recovery after spinal cord injury (SCI). Treatment with them has encouraged axon regeneration, sprouting and functional recovery in a variety of spinal cord and central nervous system injury models. The two compounds work, in part, through different mechanisms, so it is possible that their effects will be additive. In this study, we used a rat cervical partial SCI model to explore the effectiveness of a combination of anti-Nogo-A, ChABC, and rehabilitation. We found that spontaneous recovery of forelimb functions reflects the extent of the lesion on the ipsilateral side. We applied a combination treatment with acutely applied anti-Nogo-A antibody followed by delayed ChABC treatment starting at 3 weeks after injury, and rehabilitation starting at 4 weeks, to accommodate the requirement that anti-Nogo-A be applied acutely, and that rehabilitation be given after the cessation of anti-Nogo-A treatment. We found that single treatment with either anti-Nogo-A or ChABC, combined with rehabilitation, produced functional recovery of similar magnitude. The combination treatment, however, was more effective. Both single treatments produced increases in sprouting and axon regeneration, but the combination treatment produced greater increases. Anti-Nogo-A stimulated growth of a greater number of axons with a diameter of > 3 μm, whereas ChABC treatment stimulated increased growth of finer axons with varicosities. These results point to different functions of Nogo-A and chondroitin sulfate proteoglycans in axonal regeneration. The combination of anti-Nogo-A, ChABC and rehabilitation shows promise for enhancing functional recovery after SCI.

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More information

Published date: September 2013
Additional Information: © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Keywords: axon regeneration, chondroitinase, Nogo-A, plasticity, rehabilitation, spinal cord
Organisations: Biomedicine

Identifiers

Local EPrints ID: 411075
URI: https://eprints.soton.ac.uk/id/eprint/411075
ISSN: 0953-816X
PURE UUID: 71256068-64cf-44e8-847a-5a8de7aee783
ORCID for Melissa R. Andrews: ORCID iD orcid.org/0000-0001-5960-5619

Catalogue record

Date deposited: 13 Jun 2017 16:33
Last modified: 20 Jul 2019 00:28

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