title: Combination treatment with anti-Nogo-A and chondroitinase ABC is more effective than single treatments at enhancing functional recovery after spinal cord injury.
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.
authors.affiliation: Department of Clinical Neurosciences, Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, UK.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Zhao
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Andrews
authors.forename: Difei
authors.initials: D
authors.lastname: Wang
authors.forename: Philippa
authors.initials: P
authors.lastname: Warren
authors.forename: Miriam
authors.initials: M
authors.lastname: Gullo
authors.forename: Lisa
authors.initials: L
authors.lastname: Schnell
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D002574:Cervical Vertebrae; D019765:Chondroitin ABC Lyase / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D008297:Male; D009185:Myelin Proteins / Q000276:immunology*; D000070798:Nogo Proteins; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D000906:Antibodies; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat; D019765:Chondroitin ABC Lyase
keywords: Nogo-A; axon regeneration; chondroitinase; plasticity; rehabilitation; spinal cord