Axonal regeneration promoters

Adhesion molecules such as LI, neural cell adhesion molecule (N-CAM) and N-cadherin promote axonal regeneration by homophilic interactions between axons and Schwann cell surfaces (see Ch. 7). The expression of p75 (low affinity NGF receptor, Ch. 27) is also increased at the Schwann cell surface after injury. Extracellular matrix molecules, such as tenascin and proteoglycans, increase the regenerative potential of damaged peripheral nerves by binding to integrins on the axonal surface. 

Nogo-A. Treatment with IN-1 promoted axonal regeneration and behavioral recovery in rats after thoracic spinal cord injury. These exciting results have since been confirmed using local intrathecal pump infusions of recombinant IN-1 Fab fragments or novel anti-Nogo-A antibodies [9]. 

Sicotte, M., Tsatas, O., Jeong, S. Y., Cai, C-Q., He, Z. and David, S. Immunization with myelin or recombinant Nogo-66/MAG promotes axon regeneration and sprouting after corticospinal tract lesions in the spinal cord. Mol. Cell. Neurosci. 23 251-263, 2003. 

Kobayashi, N. R., Fan, D-P., Giehl, K. M., Bedard, A. M., Wiegand, S. J. and Tetzlaff, W. BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Tal-tubulin mRNA expression, and promote axonal regeneration. /. Neurosci. 17 9583-9595, 1997. 

Wildering, W.C., Hermann, P.M. and Bulloch, A.G.M. (2001) Lymnaea epidermal growth factor promotes axonal regeneration in CNS organ culture, journal of Neuroscience 21, 9345-9354. 

GrandPre, T., Li, S., and Strittmatter, S. M. (2002). Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 417, 547-551. 

Lehmann, M, Fournier, A, Selles-Navarro, I, Dergham, P, Sehok, A, Leclerc, N, Tigyi, G, McKerracher, L, Inactivation of Rho signahng pathway promotes CNS axon regeneration, J. NeuroscL, 19, 7537-7547, 1999. 

NGF infusions into the ventral hippocampus promoted axonal regeneration from the septum into the dorsal hippocampal formation, but did not induce sprouting of the nonlesioned cholinergic pathway that projects to the ventral hippocampal formation.164 Thus, as was also mentioned in Section 9.4.1.1, it is possible that NGF or other neurotrophic factors only or predominantly promote regeneration of lesioned axons in the adult brain. If so, the side effects of such treatments may not include or have limited effect on aberrant collateral sprouting of noninjured axons. One important question, which has not been resolved, is whether or how the neurotropic and guidance effects of NGF can be harnessed or even circumvented to allow a normal pattern of reinnervation and the formation of appropriate synaptic reconnections. 

Kromer, L. F. and Combrooks, C. J., Identification of trophic factors and transplanted cellular environments that promote CNS axonal regeneration, Ann. N.Y. Acad. Sci., 495, 207, 1987. 

Brecknell, J. E., Du, J. S., Muir, E., Fidler, P. S., Hlavin, M. L., Dunnett, S. B., and Fawcett, J. W., Bridge grafts of fibroblast growth factor-4-secreting schwannoma cells promote functional axonal regeneration in the nigrostriatal pathway of the adult rat, Neuroscience, 74, 775, 1996. 

---