Ramer, et al (2001): Two-tiered inhibition of axon regeneration at the dorsal root entry zone

[Wise Young]

• Ramer MS, Duraisingam I, Priestley JV and McMahon SB (2001). Two-tiered inhibition of axon regeneration at the dorsal root entry zone. J Neurosci. 21 (8): 2651-60. Summary: Glial-derived inhibitory molecules and a weak cell-body response prevent sensory axon regeneration into the spinal cord after dorsal root injury. Neurotrophic factors, particularly neurotrophin-3 (NT-3), may increase the regenerative capacity of sensory neurons after dorsal rhizotomy, allowing regeneration across the dorsal root entry zone (DREZ). Intrathecal NT-3, delivered at the time of injury, promoted an upregulation of the growth-associated protein GAP-43 primarily in large- diameter sensory profiles (which did not occur after rhizotomy alone), as well as regeneration of cholera toxin B-labeled sensory axons across the DREZ and deep into the dorsal horn. However, delaying treatment for 1 week compromised regeneration: although axons still penetrated the DREZ, growth within white matter was qualitatively and quantitatively restricted. This was not associated with an impaired cell-body response (GAP-43 upregulation was equivalent for both immediate and delayed treatments), or with astrogliosis at the DREZ, which begins almost immediately after rhizotomy, but with the delayed appearance of mature ED1-expressing phagocytes in the dorsal white matter between 1 and 2 weeks after lesion, marking the beginning of myelin breakdown. After rhizotomy with immediate NT-3 treatment, regeneration continues beyond 2 weeks, but in the dorsal gray matter rather than in the degenerating dorsal columns. The ability of NT-3 to promote regeneration across the DREZ, but not after the beginning of degeneration after delayed treatment reveals a hierarchy of inhibitory influences: the astrogliotic, but not the degenerative barrier is surmountable by NT-3 treatment. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11306618
http://www.jneurosci.org/cgi/content/full/21/8/2651
http://www.jneurosci.org/cgi/content/abstract/21/8/2651> Sensory Function Group, Center for Neuroscience Research, Guy's King's and St. Thomas' School of Biomedical Science, London SE1 1UL, United Kingdom. matt.ramer@kcl.ac.uk

[This message was edited by Wise Young on September 23, 2001 at 08:04 PM.]

[This message was edited by Wise Young on September 23, 2001 at 08:32 PM.]