Months after the spinal cord is severed in lampreys, the fish can swim again without any therapeutic intervention (Cohen et al., 1989), but they seem unique among vertebrates in being able to spontaneously reconnect damaged neurons. Nevertheless, in the wake of several research breakthroughs, there is more hope than ever for an effective treatment to help severed neuronal pathways in the spinal cord reconnect with their targets. Four main strategies for reconnecting the brain and spinal cord in humans are being investigated (see Figure 1):

1. Providing stem cells that might differentiate into new neurons to send new axons across the break (Okano et al., 2003).
2. Transplanting glial cells that promote regeneration in the CNS. Recall from Chapter 6 that olfactory receptor neurons are continually produced, and somehow the axons of the new neurons find the way to their proper targets. Specialized glial cells called olfactory ensheathing cells appear to play a central role in guiding this axon growth, so researchers tried transplanting ensheathing cells from the olfactory bulbs into spinal cord cuts in rats. In most cases, and for various forms of spinal cord damage, at least some function is restored (Raisman and Li, 2007). Efforts are under way to perfect the use of ensheathing cells to bridge across spinal cord lesions.
3. Using neurotrophic factors and/or adhesive molecules to entice the axons of surviving neurons to grow across the damaged region of spinal cord (Hendriks et al., 2004) and reconnect to their targets (Harel and Strittmatter, 2006). In dogs, a nonspecific polymer, polyethylene glycol, seems to repair broken membranes when injected into the spinal cord within a few days of injury. Dogs given this treatment were more than twice as likely to walk again (Laverty et al., 2004).
4. Transplanting “regeneration-friendly” peripheral nerves to connect the brain and lower spinal cord by forming a “bridge” around the injured spinal cord (Bernstein-Goral and Bregman, 1993). This approach centers on the observation that axons in peripheral nerves, when cut by injury, will regrow and reconnect to their targets, yet cut axons in the central nervous system almost never accomplish this feat. No one really knows why peripheral and central axons differ in this regard, but it might be possible to exploit regeneration-friendly peripheral nerves to reconnect the spinal cord.

Figure 1  Research Strategies for Reconnecting the Brain and Spinal Cord

References

Bernstein-Goral, H., and Bregman, B. S. (1993). Spinal cord transplants support the regeneration of axotomized neurons after spinal cord lesions at birth: A quantitative double-labeling study. Experimental Neurology 123: 118–132.

Cohen, A. H., Baker, M. T., and Dobrov, T. A. (1989). Evidence for functional regeneration in the adult lamprey spinal cord following transection. Brain Research 496: 368–372.

Harel, N. Y., and Strittmatter, S. M. (2006). Can generating axons recapitulate developmental guidance during recovery from spinal cord injury? Nature Reviews. Neuroscience 7: 603–616.

Hendriks, W. T., Ruitenberg, M. J., Blits, B., Boer, G. J., et al. (2004). Viral vector-mediated gene transfer of neurotrophins to promote regeneration of the injured spinal cord. Progress in Brain Research 146: 451–476.

Laverty, P. H., Leskovar, A., Breur, G. J., Coates, J. R., et al. (2004). A preliminary study of intravenous surfactants in paraplegic dogs: Polymer therapy in canine clinical SCI. Journal of Neurotrauma 21: 1767–1777.

Okano, H., Ogawa, Y., Nakamura, M., Kaneko, S., et al. (2003). Transplantation of neural stem cells into the spinal cord after injury. Seminars in Cell and Developmental Biology 14: 191–198.

Raisman, G., and Li, Y. (2007). Repair of neural pathways by olfactory ensheathing cells. Nature Reviews. Neuroscience 8: 312–319.