PMID- 10583476 OWN - NLM STAT- MEDLINE DCOM- 19991228 LR - 20190815 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 11 IP - 11 DP - 1999 Nov TI - NT-3 promotes growth of lesioned adult rat sensory axons ascending in the dorsal columns of the spinal cord. PG - 3873-83 AB - The regeneration capacity of spinal cord axons is severely limited. Recently, much attention has focused on promoting regeneration of descending spinal cord pathways, but little is known about the regenerative capacity of ascending axons. Here we have assessed the ability of neurotrophic factors to promote regeneration of sensory neurons whose central axons ascend in the dorsal columns. The dorsal columns of adult rats were crushed and either brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3) or a vehicle solution was delivered continuously to the lesion site for 4 weeks. Transganglionic labelling with cholera toxin beta subunit (CTB) was used to selectively label large myelinated Abeta fibres. In lesioned rats treated with vehicle, CTB-labelled fibres were observed ascending in the gracile fasciculus, but these stopped abruptly at the lesion site, with no evidence of sprouting or growth into lesioned tissue. No CTB-labelled terminals were observed in the gracile nucleus, indicating that the lesion successfully severed all ascending dorsal column axons. Treatment with BDNF did not promote axonal regeneration. In GDNF-treated rats fibres grew around cavities in caudal degenerated tissue but did not approach the lesion epicentre. NT-3, in contrast, had a striking effect on promoting growth of lesioned dorsal column axons with an abundance of fibre sprouting apparent at the lesion site, and many fibres extending into and beyond the lesion epicentre. Quantification of fibre growth confirmed that only in NT-3-treated rats did fibres grow into the crush site and beyond. No evidence of terminal staining in the gracile nucleus was apparent following any treatment. Thus, although NT-3 promotes extensive growth of lesioned axons, other factors may be required for complete regeneration of these long ascending projections back to the dorsal column nuclei. The intrathecal delivery of NT-3 or other neurotrophic molecules has obvious advantages in clinical applications, as we show for the first time that dorsal column axonal regeneration can be achieved without the use of graft implantation or nerve lesions. FAU - Bradbury, E J AU - Bradbury EJ AD - Neuroscience Research Centre, Guys, Kings and St Thomas School of Biomedical Sciences, Division of Physiology, Lambeth Palace Road, London E1 4NS, UK. e.bradbury@umds.ac.uk FAU - Khemani, S AU - Khemani S FAU - Von, R AU - Von R FAU - King AU - King FAU - Priestley, J V AU - Priestley JV FAU - McMahon, S B AU - McMahon SB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Gdnf protein, rat) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Neurotrophin 3) SB - IM MH - Animals MH - Axons/drug effects/*physiology MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Glial Cell Line-Derived Neurotrophic Factor MH - Male MH - Nerve Crush MH - Nerve Fibers/physiology MH - *Nerve Growth Factors MH - Nerve Regeneration MH - Nerve Tissue Proteins/pharmacology MH - Neurons, Afferent/drug effects/*physiology MH - Neuroprotective Agents/pharmacology MH - Neurotrophin 3/*pharmacology MH - Posterior Horn Cells/drug effects/*physiology MH - Rats MH - Rats, Wistar MH - Spinal Cord/drug effects/physiology/physiopathology MH - Spinal Cord Injuries/*physiopathology EDAT- 1999/12/03 00:00 MHDA- 1999/12/03 00:01 CRDT- 1999/12/03 00:00 PHST- 1999/12/03 00:00 [pubmed] PHST- 1999/12/03 00:01 [medline] PHST- 1999/12/03 00:00 [entrez] AID - ejn809 [pii] AID - 10.1046/j.1460-9568.1999.00809.x [doi] PST - ppublish SO - Eur J Neurosci. 1999 Nov;11(11):3873-83. doi: 10.1046/j.1460-9568.1999.00809.x.