China Spinal Cord Injury Network (ChinaSCINet)

For many years, scientists and doctors believed that the spinal cord is incapable of regeneration. However, in the 1990’s, many laboratories reported success in regenerating the spinal cord of animals. Because the peripheral nervous system (PNS) can regenerate and the central nervous system (CNS) apparently cannot, most of the research try to understand the underlying biological mechanisms that either inhibit or promote new growth in the spinal cord, they are making surprising discoveries, not just about how neurons and their axons grow in the central nervous system (CNS), but also about why they fail to regenerate after injury in the adult CNS. Understanding the cellular and molecular mechanisms involved in both the working and the damaged spinal cord could point the way to therapies that might prevent secondary damage, encourage axons to grow past injured areas, and reconnect vital neural circuits within the spinal cord and CNS.
The past decade of spinal cord injury (SCI) research suggests that therapies must address three main obstacles to regeneration.

Many individual therapies have been reported to overcome these obstacles to regeneration. For example, cell transplants from many sources have been reported to survive, proliferate, and bridge the injury site. Growth factors, particularly combinations of the neurotrophins, can stimulate regeneration. Many drugs have been developed to address, including Nogo antibodies, receptor proteins, and Nogo receptor antagonists. The bacterial enzyme chondroitinase(Chase) has been reported by many investigators to allow regeneration of axons associated with functional improvement. [9-11].

The most successful regenerative therapies address all the obstacles mentioned above. [12] For example, a combination of Schwann cell transplants and cAMP-enhancing drugs was reported to produce very significant regeneration and functional recovery in rats. [13] Bone marrow mesenchymal stem cells have been reported to be more effective in facilitating regeneration when combined with cAMP.[14] Chondroitinase and lithium reportedly stimulates regeneration in hemisected rat spinal cords. [15]

References

1. Reier PJ, et al. Reactive astrocyte and axonal outgrowth in the injured CNS: is gliosis really an impediment to regeneration? In: Seil FJ (ed) Neural regeneration and transplantation. Liss, New York, pp 183-209, 1989

2. Dotti, C.G., et al. The Establishment of Polarity by Hippocampal Neurons in Culture. J Neurosci 8: 1454–1468, 1988

3. Mukhopadhyay G, et al. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13:757-767, 1994

4. Chen MS, et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403:434-439, 2000

5. Cafferty W. and Strittmatter S. The Nogo–Nogo Receptor Pathway Limits a Spectrum of Adult CNS Axonal Growth. J Neurosci 26:12242–12250, 2006

6. Wang X., et al. Delayed Nogo Receptor Therapy Improves Recovery from Spinal Cord Contusion. Ann Neurol 60:540-549, 2006

7. Bradbury EJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 2002, Apr.11;416(6881):636-640

8. Yick LW, Cheung PT, So KF, Wu W. Axonal regeneration of Clarke's neurons beyond the spinal cord injury scar after treatment with chondroitinase ABC. Exp Neurol. 2003 Jul;182(1):160-8

9. Barritt AW, et al. Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci. 2006 Oct 18; 26(42):10856-67

10. Tester NJ, Howland DR. Chondroitinase ABC improves basic and skilled locomotion in spinal cord injured cats. Exp Neurol. 2008 Feb;209(2):483-96

11. Cafferty WB, et al. Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. J Neurosci. 2007 Feb 28;27(9):2176-85

12. Bunge MB and Pearse DD. Transplantation Strategies to Promote Repair of the Injured Spinal Cord. J Rehab Res Dev 40(S1):55-62, 2003

13. Pearse DD, et al. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med. 2004 Jun;10(6):610-6

14. Kim SS, et al. cAMP induces neuronal differentiation of mesenchymal stem cells via activation of extracellular signal-regulated kinase/MAPK. Neuroreport. 2005 Aug 22;16(12):1357-61

15. Yick LW, So KF, Cheung PT, Wu WT. Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. J Neurotrauma. 2004 Jul;21(7):932-43