Spinal cord injury regenerative strategies and obstacles

Current Opinion in Orthopaedics

Volumn 15, Issue 3, 2004, Pages 196-201

  Kwon, Brian K ^a   Dvorak, Marcel F ^a   Fisher, Charles G ^a   Tetzlaff, Wolfram ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Axonal regeneration; Neuroprotection; Pathophysiology

Indexed keywords

4 AMINOPYRIDINE; CYCLOSPORIN; GANGLIOSIDE GM1; GROWTH FACTOR; METHYLPREDNISOLONE; POTASSIUM CHANNEL BLOCKING AGENT; TACROLIMUS;

ACUTE DISEASE; ADOPTIVE IMMUNOTHERAPY; AXONAL INJURY; BRAIN INJURY; CELL ACTIVITY; CHRONIC DISEASE; CLINICAL EXAMINATION; CLINICAL TRIAL; CONVALESCENCE; DRUG EFFICACY; DRUG MEGADOSE; EVALUATION; HUMAN; MOLECULAR BIOLOGY; NERVE FIBER REGENERATION; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PATHOPHYSIOLOGY; PHYSICIAN; PRIORITY JOURNAL; REVIEW; SPINAL CORD INJURY; SPINAL CORD NERVE CELL; STEM CELL; TREATMENT PLANNING;

EID: 2442562721     PISSN: 10419918     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.bco.0000123488.23763.a7     Document Type: Review

References (40)

1. Kakulas BA: A review of the neuropathology of human spinal cord injury with emphasis on special features. J Spinal Cord Med 1999, 22:119-124.
2. Kwon BK, Tetzlaff W, Grauer JN, et al.: Pathophysiobgy and pharmacologic treatment of acute spinal cord injury. The Spine Journal, in press.
3. Gruner JA, Yee AK: 4-Aminopyridine enhances motor evoked potentials following graded spinal cord compression injury in rats. Brain Res 1999, 816:446-456.
4. Grijalva I, Guizar-Sahagun G, Castaneda-Hernandez G, et al.: Efficacy and safety of 4-aminopyridine in patients with long-term spinal cord injury: a randomized, double-blind, placebo-controlled trial. Pharmacotherapy 2003, 23:823-834.
5. Pharmacological therapy after acute cervical spinal cord injury. Neurosurgery 2002, 50(Suppl 3):S63-S72.
6. Geisler FH, Coleman WP, Grieco G, Poonian D: The Sygen multicenter acute spinal cord injury study. Spine 2001, 26(Suppl 24):S87-S98.
7. Hausmann ON: Post-traumatic inflammation following spinal cord injury. Spinal Cord 2003, 41:369-378.
8. Bethea JR: Spinal cord injury-induced inflammation: a dual-edged sword. Prog Brain Res 2000, 128:33-42.
9. Klusman I, Schwab ME: Effects of pro-inflammatory cytokines in experimental spinal cord injury. Brain Res 1997, 762:173-184.
10. Hauben E, Schwartz M: Therapeutic vaccination for spinal cord injury: helping the body to cure itself. Trends Pharmacol Sci 2003, 24:7-12. This review provides a recent summary of the potentially beneficial and therapeutic aspects of the neuroimmunologic and neuroinflammatory reaction to spinal cord injury. Much of this work has been pioneered by Dr. Schwartz, whose work in the area of activated macrophages has led to ongoing human clinical trials of surgically implanting autologous activated macrophages.
11. Rapalino O, Lazarov-Spiegler O, Agranov E, et al.: Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 1998, 4:814-821.
12. Hauben E, Butovsky O, Nevo U, et al.: Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J Neurosci 2000, 20:6421-6430.
13. Schwartz M: Sell Memorial Lecture. Helping the body to cure itself: immune modulation by therapeutic vaccination for spinal cord injury. J Spinal Cord Med 2003, 26(Suppl 1):S6-10.
14. Schwartz M, Hauben E: T cell-based therapeutic vaccination for spinal cord injury. Prog Brain Res 2002, 137:401-406.
15. Jones TB, Basso DM, Sodhi A, et al.: Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. J Neurosci 2002, 22:2690-2700.
16. Fee D, Crumbaugh A, Jacques T, et al.: Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury. J Neuroimmunol 2003, 136:54-66.
17. Popovich PG, Jones TB: Manipulating neuroinflammatory reactions in the injured spinal cord: back to basics. Trends Pharmacol Sci 2003, 24:13-17. This review provides a cautionary perspective on the neuroimmunologic and neuroinflammatory reactions to spinal cord injury, and summarizes the deleterious aspects of these processes. The authors point out that caution must be exercised in the manipulation of these complex responses.
18. Urist MR: Bone: formation by autoinduction. Science 1965, 150:893-899.
19. Wozney JM, Rosen V, Celeste AJ, et al.: Novel regulators of bone formation: molecular clones and activities. Science 1988, 242:1528-1534.
20. Wells JE, Hurlbert RJ, Fehlings MG, Yong VW: Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain 2003, 126:1628-1637. This is the first published report of the neuroprotective effects of minocycline in an animal model of contusion spinal cord injury. The widespread clinical use of minocycline as an antibiotic raises the possibility that such an agent could be tested in human patients in the near future.
21. Goldman SA, Nedergaard M: Erythropoietin strikes a new cord. Nat Med 2002, 8:785-787.
22. Gorio A, Gokmen N, Erbayraktar S, et al.: Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci U S A 2002, 99:9450-9455. This is the first published report of the neuroprotective effects of erythropoietin in an animal model of contusion spinal cord injury, and like minocycline, the widespread use of this drug already in humans raises the potential that it may be safely tested in human spinal cord injury.
23. Kwon BK, Tetzlaff W: Spinal cord regeneration: from gene to transplants. Spine 2001, 26(Suppl 24):S13-S22.
24. Fernandes KJ, Tetzlaff W: Gene expression in axotomized neurons: identifying the intrinsic determinants of axonal growth. In: Ingoglia NA, Murray M, eds. Axonal Regeneration in the Central Nervous System. New York: Marcel Dekker, Inc., 2000:219-266.
25. Kobayashi NR, Fan DP, Giehl KM, et al.: BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Talpha1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 1997, 17:9583-9595.
26. Kwon BK, Liu J, Messerer C, et al.: Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury. Proc Natl Acad Sci U S A 2002, 99:3246-3251.
27. Benowitz LI, Goldberg DE, Irwin N: Inosine stimulates axon growth in vitro and In the adult CNS. Prog Brain Res 2002, 137:389-399.
28. Qiu J, Cai D, Dai H, et al.: Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 2002, 34:895-903.
29. Fournier AE, GrandPre T, Strittmatter SM: Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001, 409:341-346.
30. McGee AW, Strittmatter SM: The Nogo-66 receptor: focusing myelin inhibition of axon regeneration. Trends Neurosci 2003, 26:193-198.
31. Kwon BK, Borisoff JF, Tetzlaff W: Molecular targets for intervention in spinal cord injury. Molecular Interventions 2002, 2:244-258.
32. Zheng B, Ho C, Li S, et al.: Lack of enhanced spinal regeneration in Nogo-deficient mice. Neuron 2003, 38:213-224.
33. Simonen M, Pedersen V, Weinmann O, et al.: Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury. Neuron 2003, 38:201-211.
34. Kim JE, Li S, GrandPre T, et al.: Axon regeneration in young adult mice lacking Nogo-A/B. Neuron 2003, 38:187-199.
35. Woolf CJ: No Nogo: now where to go? Neuron 2003, 38:153-156.
36. Davies SJ, Fitch MT, Memberg SP, et al.: Regeneration of adult axons in white matter tracts of the central nervous system. Nature 1997, 390:680-683.
37. Morgenstern DA, Asher RA, Fawcett JW: Chondroitin sulphate proteoglycans in the CNS injury response. Prog Brain Res 2002, 137:313-332.
38. Bradbury EJ, Moon LD, Popat RJ, et al.: Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002, 416:636-640. This paper demonstrates that by degrading aspects of the glial scar (the chondroitin sulfate proteoglycana), some axonal sprouting can be promoted with the facilitation of motor recovery in an animal model of spinal cord injury.
39. Wirth ED III, Reier PJ, Fessler RG, et al.: Feasibility and safety of neural tissue transplantation in patients with syringomyelia. J Neurotrauma 2001, 18:911-929.
40. Santos-Benito FF, Ramon-Cueto A: Olfactory ensheathing glia transplantation: a therapy to promote repair in the mammalian central nervous system. Anat Rec 2003, 271B:77-85.