TY - JOUR
T1 - Neurotrophins promote regeneration of sensory axons in the adult rat spinal cord
AU - Oudega, Martin
AU - Hagg, Theo
N1 - Funding Information:
We are grateful to Damaso Sadi for his excellent technical assistance. Our colleagues at Regeneron Pharmaceuticals (Tarrytown, NY) are much appreciated for their continuing and generous supply of BDNF and NT-3. This work was supported by a grant from the International Research Institute for Paraplegia and a Scholarship from the Medical Research Council of Canada (TH).
PY - 1999/2/13
Y1 - 1999/2/13
N2 - We have investigated the effects of nerve growth factor (NGF), brain- derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) on the intraspinal regeneration of anterogradely labeled axotomized ascending primary sensory fibers in the adult rat. These fibers were allowed to grow across a predegenerated peripheral nerve graft and back into the thoracic spinal cord. In control animals that had been infused with vehicle for two weeks into the dorsal column, 3 mm rostral to the nerve graft, essentially no fibers had extended from the nerve graft back into the spinal cord. The number of sensory fibers in the rostral end of the nerve graft was not significantly different between control and neurotrophin-infused animals. With infusion of NGF, 37 ± 2% of the fibers at the rostral end of the graft had grown up to 0.5 mm into the dorsal column white matter, 30 ± 2% up to 1 mm, 19 ± 3% up to 2 mm and 8 ± 2% up to 3 mm, i.e., the infusion site. With infusion of NT-3, sensory fiber outgrowth was similar to that seen with NGF, but with BDNF fewer fibers reached farther distances into the cord. Infusion of a mixture of all three neurotrophins did not increase the number of regenerating sensory fibers above that seen after infusion of the individual neurotrophins. These findings suggest that injured ascending sensory axons are responsive to all three neurotrophins and confirm our previous findings that neurotrophic factors can promote regeneration in the adult central nervous system.
AB - We have investigated the effects of nerve growth factor (NGF), brain- derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) on the intraspinal regeneration of anterogradely labeled axotomized ascending primary sensory fibers in the adult rat. These fibers were allowed to grow across a predegenerated peripheral nerve graft and back into the thoracic spinal cord. In control animals that had been infused with vehicle for two weeks into the dorsal column, 3 mm rostral to the nerve graft, essentially no fibers had extended from the nerve graft back into the spinal cord. The number of sensory fibers in the rostral end of the nerve graft was not significantly different between control and neurotrophin-infused animals. With infusion of NGF, 37 ± 2% of the fibers at the rostral end of the graft had grown up to 0.5 mm into the dorsal column white matter, 30 ± 2% up to 1 mm, 19 ± 3% up to 2 mm and 8 ± 2% up to 3 mm, i.e., the infusion site. With infusion of NT-3, sensory fiber outgrowth was similar to that seen with NGF, but with BDNF fewer fibers reached farther distances into the cord. Infusion of a mixture of all three neurotrophins did not increase the number of regenerating sensory fibers above that seen after infusion of the individual neurotrophins. These findings suggest that injured ascending sensory axons are responsive to all three neurotrophins and confirm our previous findings that neurotrophic factors can promote regeneration in the adult central nervous system.
KW - Axotomy
KW - Brain-derived neurotrophic factor
KW - Conditioning lesion
KW - Nerve growth factor
KW - Neurotrophin-3
KW - Peripheral nerve graft
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U2 - 10.1016/S0006-8993(98)01314-6
DO - 10.1016/S0006-8993(98)01314-6
M3 - Article
C2 - 10082829
AN - SCOPUS:0033550707
VL - 818
SP - 431
EP - 438
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -