Neurotrophin-3-mediated regeneration and recovery of proprioception following dorsal rhizotomy.
Injured dorsal root axons fail to regenerate into the adult spinal cord, leading to permanent sensory loss. We investigated the ability of intrathecal neurotrophin-3 (NT3) to promote axonal regeneration across the dorsal root entry zone (DREZ) and functional recovery in adult rats. Quantitative electron microscopy showed robust penetration of CNS tissue by regenerating sensory axons treated with NT3 at 1 and 2 weeks postrhizotomy. Light and electron microscopical anterograde tracing experiments showed that these axons reentered appropriate and ectopic laminae of the dorsal horn, where they formed vesicle-filled synaptic buttons. Cord dorsum potential recordings confirmed that these were functional. In behavioral studies, NT3-treated (but not untreated or vehicle-treated) rats regained proprioception. Recovery depended on NT3-mediated sensory regeneration: preventing regeneration by root excision prevented recovery. NT3 treatment allows sensory axons to overcome inhibition present at the DREZ and may thus serve to promote functional recovery following dorsal root avulsions in humans.
Ramer
Matt S
MS
CORD (Collaboration on Repair Discoveries), The University of British Columbia, Biosciences Building, 6270 University Boulevard, Vancouver, British Columbia V6T 1Z4, Canada.
Bishop
Thomas
T
Dockery
Peter
P
Mobarak
Makarim S
MS
O'Leary
Donald
D
Fraher
John P
JP
Priestley
John V
JV
McMahon
Stephen B
SB
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002772:Cholera Toxin / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D020933:Neurotrophin 3 / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011434:Proprioception / Q000187:drug effects / Q000502:physiology; D011843:Radiculopathy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D019051:Rhizotomy; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000254:growth & development / Q000293:injuries; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D020933:Neurotrophin 3; D002772:Cholera Toxin