title: Administration of chondroitinase ABC rostral or caudal to a spinal cord injury site promotes anatomical but not functional plasticity.
abstract: Growth-inhibitory chondroitin sulfate proteoglycans (CSPG) are a primary target for therapeutic strategies after spinal cord injury because of their contribution to the inhibitory nature of glial scar tissue, a major barrier to successful axonal regeneration. Chondroitinase ABC (ChABC) digestion of CSPGs promotes axonal regeneration beyond a lesion site with subsequent functional improvement. ChABC also has been shown to promote sprouting of spared fibers but it is not clear if functional recovery results from such plasticity. Here we sought to better understand the roles rostral or caudal sprouting may play in ChABC-mediated functional improvement. To achieve this, ChABC or vehicle was injected rostral or caudal to a unilateral C5 injury. When injected rostral to a hemisection, ChABC promoted significant sprouting of 5HT+ fibers into dorsal and ventral horns. When ChABC was injected into tissue caudal to a hemisection, no additional sprouting was observed. When injected caudal to a hemicontusion injury, ChABC promoted sprouting of 5HT+ fibers into the ventral horn but not the dorsal horn. None of this sprouting resulted in a change in the synaptic component synapsin, nor did it impact performance in behavioral tests assessing motor function. These data suggest that ChABC-mediated sprouting of spared fibers does not necessarily translate into functional recovery.
authors: Department of Neurobiology and Anatomy, Drexel University College of Medicine , Philadelphia, Pennsylvania, USA.
authors: Veronica J
authors: VJ
authors: Tom
authors: Rachel
authors: R
authors: Kadakia
authors: Lauren
authors: L
authors: Santi
authors: John D
authors: JD
authors: Houlé
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000502:physiology; D019765:Chondroitin ABC Lyase / Q000494:pharmacology* / Q000627:therapeutic use; D002921:Cicatrix / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005911:Gliosis / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D020439:Growth Cones / Q000187:drug effects* / Q000378:metabolism; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D010243:Paralysis / Q000188:drug therapy; D011903:Raphe Nuclei / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D016704:Synapsins / Q000378:metabolism
chemical_list: D006131:Growth Inhibitors; D016704:Synapsins; D012701:Serotonin; D019765:Chondroitin ABC Lyase