title: Chondroitinase ABC-mediated plasticity of spinal sensory function.
abstract: Experimental therapeutics designed to enhance recovery from spinal cord injury (SCI) primarily focus on augmenting the growth of damaged axons by elevating their intrinsic growth potential and/or by nullifying the influence of inhibitory proteins present in the mature CNS. However, these strategies may also influence the wiring of intact pathways. The direct contribution of such effects to functional restoration after injury has been mooted, but as yet not been described. Here, we provide evidence to support the hypothesis that reorganization of intact spinal circuitry enhances function after SCI. Adult rats that underwent unilateral cervical spared-root lesion (rhizotomy of C5, C6, C8, and T1, sparing C7) exhibited profound sensory deficits for 4 weeks after injury. Delivery of a focal intraspinal injection of the chondroitin sulfate proteoglycan-degrading enzyme chondroitinase ABC (ChABC) was sufficient to restore sensory function after lesion. In vivo electrophysiological recordings confirm that behavioral recovery observed in ChABC-treated rats was consequent on reorganization of intact C7 primary afferent terminals and not regeneration of rhizotomized afferents back into the spinal cord within adjacent segments. These data confirm that intact spinal circuits have a profound influence on functional restoration after SCI. Furthermore, comprehensive understanding of these targets may lead to therapeutic interventions that can be spatially tailored to specific circuitry, thereby reducing unwanted maladaptive axon growth of distal pathways.
authors.affiliation: Neurorestoration Group, The Wolfson Centre for Age-Related Diseases, King's College London, London SE11UL, United Kingdom.
authors.forename: William B J
authors.initials: WB
authors.lastname: Cafferty
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Bradbury
authors.forename: Malcolm
authors.initials: M
authors.lastname: Lidierth
authors.forename: Martyn
authors.initials: M
authors.lastname: Jones
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Duffy
authors.forename: Sophie
authors.initials: S
authors.lastname: Pezet
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000344:Afferent Pathways / Q000187:drug effects / Q000201:enzymology / Q000293:injuries; D000818:Animals; D019765:Chondroitin ABC Lyase / Q000378:metabolism / Q000494:pharmacology*; D011508:Chondroitin Sulfate Proteoglycans / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D019051:Rhizotomy; D012678:Sensation Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries; D016896:Treatment Outcome
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D019765:Chondroitin ABC Lyase