Myelin contains molecules that can inhibit the growth and regeneration of axons. Neutralizing the activity of these inhibitors can enhance axon regeneration in the adult mammalian central nervous system (CNS). The complexity of the CNS-immune system interactions after CNS trauma is now beginning to be better understood. Recent studies indicate that both cell-mediated and antibody-mediated immune responses can help in promoting axon regeneration after CNS injury. It is hoped that such advances will lead to the development of safe and effective vaccine and cytokine treatments for spinal cord injuries.
Amitabh G, Wiers B, Liu A, Rothbard J, Fathman CG. 1992. Amelioration of autoimmune encephalomyelitis by myelin basic protein synthetic peptide-induced anergy. Science258:1491-1494.
2.
Asensio VC, Campbell IL. 1999. Chemokines in the CNS: plurifunctional mediators in diverse states. Trends Neurosci22:504-512.
3.
Bahr M, Przyrembel C. 1995. Myelin from peripheral and central nervous system is a non-permissive substrate for retinal ganglion cell axons. Exp Neurol134:87-93.
4.
Bandtlow CE, Schwab ME. 2000. NI-35/250/Nogo-A: a neurite growth inhibitor rstricting structural plasticity and regeneration of nerve fibers in the adult vertebrate CNS. GLIA29:175-181.
5.
Bartholdi D, Schwab ME. 1997. Expression of pro-inflammatory cytokines and chemokines mRNA upon experimental spinal cord injury in mouse: an in situ hybridization study. Eur J Neurosci9:1422-1438.
6.
Benfey M, Aguayo AJ. 1982. Extensive elongation of axons from rat brain into peripheral nerve grafts. Nature11:150-152.
7.
Bethea JR, Nagashima H, Acosta MC, Briceno C, Gomez F, Marcillo AE, and others. 1999. Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma16:851-863.
8.
Beuche W, Friede RL. 1984. The role of non-resident cells in Wallerian degeneration. J Neurocytol13:767-796.
9.
Bignami A, Ralston HJ III. 1969. The cellular reaction to Wallerian degeneration in the central nervous system of the cat. Brain Res13:444-461.
10.
Bisby MA, Chen S. 1990. Delayed Wallerian degeneration in sciatic nerves of C57BL/Ola mice is associated with impaired regeneration of sensory axons. Brain Res530:117-120.
11.
Blight AR. 1994. Effects of silica on the outcome from experimental spinal cord injury: implications of macrophages in secondary tissue damage. Neuroscience60:263-273.
12.
Bregman BS, Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME. 1995. Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature378:498-501.
13.
Brown MC, Lunn ER, Perry VH. 1992. Consequences of slow Wallerian degeneration for regenerating motor and sensory axons. J Neurobiol23:521-536.
14.
Brown MC, Perry VH, Hunt SP, Lapper SR. 1994. Further studies on motor and sensory nerve regeneration in mice with delayed Wallerian degeneration. Eur J Neurosci6:420-428.
15.
Bruck W. 1997. The role of macrophages in Wallerian degeneration. Brin Pathol7:741-752.
16.
Cardelli D, Schwab ME. 1991. Regeneration of lesioned septohippocampal acetylcholinesterase-positive axons improved by antibodies against the myelin-associated neurite growth inhibitor NI-35/250. Eur J Neurosci3:825-832.
17.
Caroni P, Schwab ME. 1988a. Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron1:85-96.
18.
Caroni P, Schwab ME. 1988b. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol106:1281-1288.
19.
Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillman AA, and others. 2000. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature403:434-439.
20.
Chen S, Bisby MA. 1993. Impaired motor axon regeneration in the C57BL/Ola mouse. J Comp Neurol333:449-454.
21.
Cohen IR, Schwartz M. 1999. Autoimmune maintenance and neuro-protection of the central nervous system. J Neuroimmunol100:111-114.
22.
David S, Aguayo AJ. 1981. Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science214:931-933.
23.
David S, Aguayo AJ. 1985. Axonal regeneration after crush injury of rat central nervous system fibers innervating peripheral nerve grafts. J Neurocytol14:1-12.
24.
David S, Bouchard C, Tsatas O, Giftochristos N. 1990. Macrophages can modify the non-permissive nature of the adult mammalian central nervous system. Neuron5:463-469.
25.
David S, Braun PE, Jackson DL, Kottis V, McKerracher L. 1995. Laminin overrides the inhibitory effects of peripheral nervous system and central nervous system myelin-derived inhibitors of neurite growth. J Neurosci Res42:594-602.
26.
De Bellard ME, Tang S, Mukhopadhyay G, Shen YI, Filbin MT. 1996. Myelin-associated glycoprotein inhibits axonal regeneration from a variety of neurons via interaction with a sialoglycoprotein. Mol Cell Neurosci7:89-101.
27.
Dejana E, Corada M, Lamugnani MG. 1995. Endothelial cell-to-cell junctions. FASEB J9:910-918.
28.
During MJ, Symes CW, Lawlor PA, and others. 2000. An oral vaccine against NMDAR1 with efficacy in experimental stoke and epilepsy. Science287:1453-1459.
29.
Fritz RB, Jen Chou C-H, McFarlin DE. 1983. Relapsing murine experimental allergic encephalomyelitis induced by myelin basic protein. J Immunol130:1024-1026.
30.
George R, Griffin JW. 1994. Delayed macrophage responses and myelin clearance during Wallerian degeneration in the central nervous system: the dorsal radiculotomy model. Exp Neurol129:225-236.
31.
Goverman J, Brabb T, Paez A, Harrington C, van Dassow P. 1997. Initiation and regulation of CNS autoimmunity. Crit Rev Immunol17:469-480.
32.
GrandPré T, Nakamura F, Vartanian T, Strittmatter SM. 2000. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature403:439-444.
33.
Gregson NA. 1989. Lysolipids and membrane damage: lysolecithin and its interaction with myelin. Biochem Soc Trans17:280-283.
34.
Griffin JW, George R, Lobato C, Tyor WR, Yan LC, Glass JD. 1992. Macrophage responses and myelin clearance during Wallerian degeneration: relevance to immune-mediated demyelination. J Neuroimmunol40:153-166.
35.
Hagg T, Manthorpe M, Vahlsing HL, Varon S. 1988. Delayed treatment with nerve growth factor reverses the apparent loss of cholinergic neurons after acute brain damage. Exp Neurol101:303-312.
36.
Hall SM. 1972. The effect of injections of lysophosphatidylcholine into white matter of the adult mouse spinal cord. J Cell Sci10:535-546.
37.
Hickey WF, Gonatas NK, Kimura H, Wilson DB. 1983. Identification and quantification of T lymphocyte subsets found in the spinal cord of the Lewis rat during experimental allergic encephalomyelitis. J Immunol131:2805-2809.
38.
Huang DW, McKerracher L, Braun PE, David S. 1999. A therapeutic vaccine approach to stimulate axon regeneration in the adult mammalian spinal cord. Neuron24:639-647.
39.
Jeffery ND, Blakemore WF. 1995. Remyelination of mouse spinal cord axon demyelinated by local injection of lysolecithin. J Neurocytol24:775-781.
40.
Lazarov-Spiegler O, Solomon AS, Schwartz M. 1998. Peripheral nerve-stimulated macrophages simulate a peripheral nerve-like regenerative response in rat transected optic nerve. GLIA24:329-337.
41.
Lazarov-Spiegler O, Solomon AS, Zeev-Brann AB, Hirschberg DL, Lavie V, Schwartz M. 1996. Transplantation of activated macrophages overcomes central nervous system regrowth failure. FASEB J10:1296-1302.
42.
Ley K. 1996. Molecular mechanisms of leukocyte recruitment in the inflammatory process. Cardiovasc Res32:733-742.
43.
Li M, Shibata A, Li C, Braun PE, McKerracher L, Roder J, and others. 1996. Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse. J Neurosci Res46:404-414.
44.
Liu KM, Shen CL. 1985. Ultrastructural sequence of myelin breakdown during Wallerian degeneration in the rat optic nerve. Cell Tissue Res242:245-256.
45.
McKerracher L, David S, Jackson DL, Kottis V, Dunn RJ, Braun PE. 1994. Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron13:805-811.
46.
Miklossy J, Van der Loos H. 1991. The long-distance effects of brain lesions: visualization of myelinated pathways in the human brain using polarizing and fluorescence microscopy. J Neuropathol Exp Neurol50:1-15.
47.
Mukhopadhyay G, Doherty P, Walsh FS, Crocker PR, Filbin MT. 1994. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron13:757-767.
Ousman S, David S. 2000. Lysophosphatidylcholine induces rapid recruitment and activation of macrophages in the adult mouse spinal cord. GLIA30:92-104.
50.
Owens T, Sriram S. 1995. The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis. Neurol Clin13:51-73.
51.
Perry VH, Brown MC, Gordon S. 1987. The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration. J Exp Med165:1218-1223.
52.
Popovich PG, Guan Z, Wei P, Huitinga I, van Rooijen N, Stokes BT. 1999. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol158:351-365.
53.
Popovich PG, Wei P, Stokes BT. 1997. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol377:443-464.
54.
Prewitt CM, Niesman IR, Kane CJ, Houle JD. 1997. Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord. Exp Neurol148:433-443.
55.
Prinjha R, Moore SE, Vinson M, Blake S, Morrow R, Christie G, and others. 2000. Neurobiology: inhibitor of neurite outgrowth in humans. Nature403:383-384.
56.
Rabchevsky AG, Streit WJ. 1997. Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res47:34-48.
57.
Ramón y Cajal S.1928. Degeneration and regeneration in the nervous system. Translated and edited by R. M. May. New York: Hafner.
58.
Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, and others. 1998. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nature Med4:814-821.
59.
Rivero VE, Maccioni M, Bucher AE, Roth GA, Riera CM. 1997. Suppression of experimental autoimmune encephalomyelitis (EAE) by intraperitoneal administration of soluble myelin antigens in Wistar rats. J Neuroimmunol72:3-10.
60.
Rodriguez M. 1991. Immunoglobulins stimulate central nervous system remyelination: electron microscopic and morphometric analysis of proliferating cells. Lab Invest64:358-370.
61.
Rodriguez M, Lennon VA, Benveniste EN, Merrill JE. 1987. Remyelination by oligodendrocytes stimulated by antiserum to spinal cord. J Neuropathol Exp Neurol46:84-95.
62.
Rodriguez M, Oleszak E, Leibowitz J. 1987. Theiler’s murine encephalomyelitis: a model of demyelination and persistence of virus. Crit Rev Immunol7:325-365.
63.
Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, and others. 1999. Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature400:173-177.
64.
Schnell L, Fearn S, Klassen H, Schwab ME, Perry VH. 1999. Acute inflammatory responses to mechanical lesions in the CNS: differences between brain and spinal cord. Eur J Neurosci11:3648-3658.
65.
Schnell L, Schneider R, Kolbeck R, Barde YA, Schwab ME. 1994. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature367:170-173.
66.
Schnell L, Schwab ME. 1990. Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature343:269-272.
67.
Shibata A, Wright MV, David S, McKerracher L, Braun PE, Kater SB. 1998. Axonal and dendritic growth cones respond differently to the inhibitory cues expressed by oligodendrocytes. J Cell Biol142:191-202.
68.
Steinman L. 1999. Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system. Cell85:299-302.
69.
Stoll G, Griffin JW, Li CY, Trapp BD. 1989. Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation. J Neurocytol18:671-683.
70.
Stoll G, Trapp BD, Griffin JW. 1989. Macrophage function during Wallerian degeneration of rat optic nerve: clearance of degenerating myelin and Ia expression. J Neurosci9:2327-2335.
71.
Streit WJ, Graeber MB. 1993. Heterogeneity of microglial and perivascular cell populations: insights gained from the facial nucleus paradigm. GLIA7:68-74.
72.
Streit WJ, Semple-Rowland SL, Hurley SD, Miller RC, Popovich PG, Stokes BT. 1998. Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis. Exp Neurol152:74-87.
73.
Swanborg RH. 1995. Experimental autoimmune encephalomyelitis in rodents as a model for human demyelinating disease. Clin Immunol Immunopathol77:3-13.
74.
Tetzlaff W, Alexander SW, Miller FD, Bisby M. 1991. Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43. J Neurosci11:2528-2544.
75.
Tonegawa SMS. 1997. Tolerance induction and autoimmune encephalomyelitis amelioration after administration of myelin basic protein-derived peptide. J Exp Med186:507-517.
76.
Tran EH, Hoekstra K, van Rooijen N, Dijkstra CD, Owens T. 1998. Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice. J Immunol161:3767-3775.
77.
Traugott U, Raine CS, McFarlin DE. 1985. Acute experimental allergic encephalomyelitis in the mouse: immunopathology of the developing lesion. Cell Immunol91:240-254.
78.
Tsunoda I, Fujinami R. 1996. Two models for multiple sclerosis: experimental allergic encephalomyelitis and Theiler’s murine encephalomyelitis virus. J Neuropathol Exp Neurol55:673-686.
79.
Vidal-Sanz M, Bray GM, Villegas-Perez MP, Thanos S, Aguayo AJ. 1987. Axonal regeneration and synapse formation in the superior colliculus by retinal ganglion cells in the adult rat. J Neurosci7:2894-2909.
80.
Weiner LH, Friedman A, Miller A, Khry SJ, al-Sabbagh A, Santos L, and others. 1994. Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu Rev Immunol12:809-837.
81.
Ye JH, Houle JD. 1997. Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol143:70-81.
