Functional regeneration of sensory axons into the adult spinal cord.
The arrest of dorsal root axonal regeneration at the transitional zone between the peripheral and central nervous system has been repeatedly described since the early twentieth century. Here we show that, with trophic support to damaged sensory axons, this regenerative barrier is surmountable. In adult rats with injured dorsal roots, treatment with nerve growth factor (NGF), neurotrophin-3 (NT3) and glial-cell-line-derived neurotrophic factor (GDNF), but not brain-derived neurotrophic factor (BDNF), resulted in selective regrowth of damaged axons across the dorsal root entry zone and into the spinal cord. Dorsal horn neurons were found to be synaptically driven by peripheral nerve stimulation in rats treated with NGF, NT3 and GDNF, demonstrating functional reconnection. In behavioural studies, rats treated with NGF and GDNF recovered sensitivity to noxious heat and pressure. The observed effects of neurotrophic factors corresponded to their known actions on distinct subpopulations of sensory neurons. Neurotrophic factor treatment may thus serve as a viable treatment in promoting recovery from root avulsion injuries. I
Ramer
M S
MS
Neuroscience Research Centre, Guy's, King's and St. Thomas' School of Biomedical Sciences, London, UK. matt.ramer@kcl.ac.uk
Priestley
J V
JV
McMahon
S B
SB
D000344:Afferent Pathways; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009409:Nerve Crush; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D020933:Neurotrophin 3 / Q000494:pharmacology; D010146:Pain; D010525:Peripheral Nerves / Q000502:physiology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D019051:Rhizotomy; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D020932:Nerve Growth Factor