title: Examination of the combined effects of chondroitinase ABC, growth factors and locomotor training following compressive spinal cord injury on neuroanatomical plasticity and kinematics.
abstract: While several cellular and pharmacological treatments have been evaluated following spinal cord injury (SCI) in animal models, it is increasingly recognized that approaches to address the glial scar, including the use of chondroitinase ABC (ChABC), can facilitate neuroanatomical plasticity. Moreover, increasing evidence suggests that combinatorial strategies are key to unlocking the plasticity that is enabled by ChABC. Given this, we evaluated the anatomical and functional consequences of ChABC in a combinatorial approach that also included growth factor (EGF, FGF2 and PDGF-AA) treatments and daily treadmill training on the recovery of hindlimb locomotion in rats with mid thoracic clip compression SCI. Using quantitative neuroanatomical and kinematic assessments, we demonstrate that the combined therapy significantly enhanced the neuroanatomical plasticity of major descending spinal tracts such as corticospinal and serotonergic-spinal pathways. Additionally, the pharmacological treatment attenuated chronic astrogliosis and inflammation at and adjacent to the lesion with the modest synergistic effects of treadmill training. We also observed a trend for earlier recovery of locomotion accompanied by an improvement of the overall angular excursions in rats treated with ChABC and growth factors in the first 4 weeks after SCI. At the end of the 7-week recovery period, rats from all groups exhibited an impressive spontaneous recovery of the kinematic parameters during locomotion on treadmill. However, although the combinatorial treatment led to clear chronic neuroanatomical plasticity, these structural changes did not translate to an additional long-term improvement of locomotor parameters studied including hindlimb-forelimb coupling. These findings demonstrate the beneficial effects of combined ChABC, growth factors and locomotor training on the plasticity of the injured spinal cord and the potential to induce earlier neurobehavioral recovery. However, additional approaches such as stem cell therapies or a more adapted treadmill training protocol may be required to optimize this repair strategy in order to induce sustained functional locomotor improvement.
authors.affiliation: Multidisciplinary Team in Locomotor Rehabilitation of the Canadian Institutes of Health Research (CIHR) and Groupe de Recherche sur le Système Nerveux Central (GRSNC) of the Fonds de Recherche du Québec - Santé (FRQS), Department of Physiology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Olivier
authors.initials: O
authors.lastname: Alluin
authors.affiliation: Multidisciplinary Team in Locomotor Rehabilitation of the Canadian Institutes of Health Research (CIHR) and Groupe de Recherche sur le Système Nerveux Central (GRSNC) of the Fonds de Recherche du Québec - Santé (FRQS), Department of Physiology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Hugo
authors.initials: H
authors.lastname: Delivet-Mongrain
authors.affiliation: The Department of Physiology and Pathophysiology and the Spinal Cord Research Center, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Marie-Krystel
authors.initials: MK
authors.lastname: Gauthier
authors.affiliation: Department of Surgery and Spinal Program, University of Toronto; Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
authors.affiliation: Multidisciplinary Team in Locomotor Rehabilitation of the Canadian Institutes of Health Research (CIHR) and Groupe de Recherche sur le Système Nerveux Central (GRSNC) of the Fonds de Recherche du Québec - Santé (FRQS), Department of Physiology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Rossignol
authors.affiliation: The Department of Physiology and Pathophysiology and the Spinal Cord Research Center, University of Manitoba, Winnipeg, Manitoba, Canada; Regenerative Medicine Program and Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
authors.forename: Soheila
authors.initials: S
authors.lastname: Karimi-Abdolrezaee
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage / Q000502:physiology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000502:physiology*; D008124:Locomotion; D009068:Movement; D009409:Nerve Crush; D009416:Nerve Regeneration; D009473:Neuronal Plasticity; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D019765:Chondroitin ABC Lyase