Need for a paradigm shift in therapeutic approaches to CNS injury

Expert Review of Neurotherapeutics

Volumn 12, Issue 4, 2012, Pages 409-420

  Wootla, Bharath ^a   Denic, Aleksandar ^a   Warrington, Arthur E ^a   Rodriguez, Moses ^a,b  

^a MAYO CLINIC   (United States)

^b MAYO GRADUATE SCHOOL   (United States)

Author keywords

Alzheimer's disease; antibodies; brain injury; catalytic antibodies; CNS injury; ischemia; multiple sclerosis; natural autoantibodies; spinal cord injury; stroke; therapeutic strategies

Indexed keywords

ALEMTUZUMAB; AUTOANTIBODY; AUTOANTIBODY LINGO 1; BAN 2401; BAPINEUZUMAB; DACLIZUMAB; GAMMA GUARD; GANTENERUMAB; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M ANTIBODY; MONOCLONAL ANTIBODY; POLYCLONAL ANTIBODY; PONEZUMAB; RECOMBINANT ANTIBODY; RECOMBINANT ANTIBODY HIGM12; RECOMBINANT ANTIBODY HIGM22; RECOMBINANT PLASMINOGEN ACTIVATOR; RILUZOLE; RITUXIMAB; SOLANEZUMAB; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ANTIBODY SPECIFICITY; ASTROCYTE; B LYMPHOCYTE; BRAIN ISCHEMIA; CELL DAMAGE; CELL DEATH; DRUG BINDING; DRUG SYNTHESIS; HUMAN; HYDROLYSIS; IMMUNOMODULATION; MICROENVIRONMENT; MICROGLIA; MULTIPLE SCLEROSIS; NERVE CELL; NERVE FIBER; NERVE REGENERATION; NERVOUS SYSTEM INJURY; NEUROPROTECTION; NONHUMAN; OLIGODENDROGLIA; PATHOGENESIS; REMYELINIZATION; REVIEW; SPINAL CORD INJURY; TISSUE REPAIR;

ANIMALS; AUTOANTIBODIES; CENTRAL NERVOUS SYSTEM DISEASES; HUMANS;

EID: 84860309490     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/ern.12.24     Document Type: Review

References (131)

1. Kelley KW, Johnson RW, Dantzer R. Immunology discovers physiology. Vet Immunol. Immunopathol. 43(1-3), 157-165 (1994). (Pubitemid 24327540)
2. Lawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39(1), 151-170 (1990).
3. Sievers J, Parwaresch R, Wottge HU. Blood monocytes and spleen macrophages differentiate into microglia-like cells on monolayers of astrocytes: Morphology. Glia 12(4), 245-258 (1994). Provided evidence that blood monocytes and spleen macrophages differentiate into microglia.
4. Kitamura T, Miyake T, Fujita S. Genesis of resting microglia in the gray matter of mouse hippocampus. J. Comp. Neurol. 226(3), 421-433 (1984). (Pubitemid 14094318)
5. Schelper RL, Adrian EK Jr. Non-specific esterase activity in reactive cells in injured nervous tissue labeled with 3H-thymidine or 125iododeoxyuridine injected before injury. J. Comp. Neurol. 194(4), 829-844 (1980). (Pubitemid 11209686)
6. Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726), 1314-1318 (2005). Showed that blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. (Pubitemid 40746128)
7. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8(1), 57-69 (2007). (Pubitemid 46011999)
8. Butovsky O, Talpalar AE, Ben-Yaakov K, Schwartz M. Activation of microglia by aggregated b-amyloid or lipopolysaccharide impairs MHC-II expression and renders them cytotoxic whereas IFN-g and IL-4 render them protective. Mol. Cell Neurosci. 29(3), 381-393 (2005). (Pubitemid 40799211)
9. Hanisch UK, Kettenmann H. Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10(11), 1387-1394 (2007). (Pubitemid 350014685)
10. Barres BA. The mystery and magic of glia: A perspective on their roles in health and disease. Neuron 60(3), 430-440 (2008).
11. McDonald JW, Sadowsky C. Spinal-cord injury. Lancet 359(9304), 417-425 (2002). (Pubitemid 34158956)
12. Iadecola C, Anrather J. The immunology of stroke: From mechanisms to translation. Nat. Med. 17(7), 796-808 (2011).
13. Larner AJ, Doran M. Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin-1 gene. J. Neurol. 253(2), 139-158 (2006). (Pubitemid 43255883)
14. Obulesu M, Venu R, Somashekhar R. Tau mediated neurodegeneration: An insight into Alzheimer's disease pathology. Neurochem. Res. 36(8), 1329-1335 (2011).
15. Gurney ME, Liu R, Althaus JS, Hall ED, Becker DA. Mutant CuZn superoxide dismutase in motor neuron disease. J. Inherit. Metab. Dis. 21(5), 587-597 (1998). (Pubitemid 28391510)
16. Morrison BM, Morrison JH. Amyotrophic lateral sclerosis associated with mutations in superoxide dismutase: A putative mechanism of degeneration. Brain Res. Rev. 29(1), 121-135 (1999). (Pubitemid 29016082)
17. Siddique T, Nijhawan D, Hentati A. Familial amyotrophic lateral sclerosis. J. Neural. Transm. Suppl. 49, 219-233 (1997). (Pubitemid 27351490)
18. Cluskey S, Ramsden DB. Mechanisms of neurodegeneration in amyotrophic lateral sclerosis. Mol. Pathol. 54(6), 386-392 (2001). (Pubitemid 34025253)
19. Neumann M, Sampathu DM, Kwong LK et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796), 130-133 (2006). (Pubitemid 44547757)
20. Valdmanis PN, Daoud H, Dion PA, Rouleau GA. Recent advances in the genetics of amyotrophic lateral sclerosis. Curr. Neurol. Neurosci. Rep. 9(3), 198-205 (2009).
21. Stewart H, Rutherford NJ, Briemberg H et al. Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p. Acta Neuropathol. 123(3), 409-417 (2012).
22. Kurtzke JF, Hyllested K. Multiple sclerosis in the Faroe Islands and the lack of protection by exposure in infancy. Neuroepidemiology 11(2), 90-99 (1992).
23. Orton SM, Herrera BM, Yee IM et al. Sex ratio of multiple sclerosis in Canada: A longitudinal study. Lancet Neurol. 5(11), 932-936 (2006). (Pubitemid 44556546)
24. Wallin MT, Page WF, Kurtzke JF. Multiple sclerosis in US veterans of the Vietnam era and later military service: Race, sex, and geography. Ann. Neurol. 55(1), 65-71 (2004). (Pubitemid 38067362)
25. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N. Engl. J. Med. 343(13), 938-952 (2000).
26. Weinshenker BG, Bass B, Rice GP et al. The natural history of multiple sclerosis: A geographically based study. I. Clinical course and disability. Brain 112(Pt 1), 133-146 (1989). (Pubitemid 19056478)
27. Hagg T, Oudega M. Degenerative and spontaneous regenerative processes after spinal cord injury. J. Neurotrauma. 23(3-4), 264-280 (2006). (Pubitemid 43726309)
28. Silver J, Miller JH. Regeneration beyond the glial scar. Nat. Rev. Neurosci. 5(2), 146-156 (2004). (Pubitemid 38160289)
29. Fitch MT, Doller C, Combs CK, Landreth GE, Silver J. Cellular and molecular mechanisms of glial scarring and progressive cavitation: In vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J. Neurosci. 19(19), 8182-8198 (1999). (Pubitemid 30226738)
30. Leal-Filho MB. Spinal cord injury: From inflammation to glial scar. Surg. Neurol. Int. 2, 112 (2011).
31. Zhang H, Muramatsu T, Murase A, Yuasa S, Uchimura K, Kadomatsu K. N-acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury. Glycobiology 16(8), 702-710 (2006). (Pubitemid 44288236)
32. Lo EH. A new penumbra: Transitioning from injury into repair after stroke. Nat. Med. 14(5), 497-500 (2008). (Pubitemid 351655209)
33. LaFerla FM, Green KN, Oddo S. Intracellular amyloid-b in Alzheimer's disease. Nat. Rev. Neurosci. 8(7), 499-509 (2007).
34. Abe N, Cavalli V. Nerve injury signaling. Curr. Opin. Neurobiol. 18(3), 276-283 (2008).
35. David S, Aguayo AJ. Axonal elongation into peripheral nervous system "bridges" after central nervous system injury in adult rats. Science 214(4523), 931-933 (1981). Demonstrated that the regenerative potential of central neurons is expressed when the CNS glial environment is changed to that of the peripheral nervous system. (Pubitemid 12220099)
36. Fitch MT, Silver J. CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp. Neurol. 209(2), 294-301 (2008). (Pubitemid 351174127)
37. Yiu G, He Z. Glial inhibition of CNS axon regeneration. Nat. Rev. Neurosci. 7(8), 617-627 (2006). (Pubitemid 44106744)
38. Benson MD, Romero MI, Lush ME, Lu QR, Henkemeyer M, Parada LF. Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth. Proc. Natl Acad. Sci. USA 102(30), 10694-10699 (2005). (Pubitemid 41061616)
39. Lee JK, Geoffroy CG, Chan AF et al. Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 66(5), 663-670 (2010).
40. Shen Y, Tenney AP, Busch SA et al. PTPs is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 326(5952), 592-596 (2009).
41. Zheng B, Atwal J, Ho C et al. Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo. Proc. Natl Acad. Sci. USA 102(4), 1205-1210 (2005). (Pubitemid 40170750)
42. Lobato RD. Historical vignette of Cajal's work 'Degeneration and regeneration of the nervous system' with a reflection of the author. Neurocirugia (Astur.) 19(5), 456-468 (2008).
43. Tom VJ, Steinmetz MP, Miller JH, Doller CM, Silver J. Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury. J. Neurosci. 24(29), 6531-6539 (2004). (Pubitemid 38971701)
44. Hur EM, Yang IH, Kim DH et al. Engineering neuronal growth cones to promote axon regeneration over inhibitory molecules. Proc. Natl Acad. Sci. USA 108(12), 5057-5062 (2011). Proposed nonmuscle myosin II and growth cone cytoskeletal components as effective targets for promoting axon regeneration.
45. Davies SJ, Fitch MT, Memberg SP, Hall AK, Raisman G, Silver J. Regeneration of adult axons in white matter tracts of the central nervous system. Nature 390(6661), 680-683 (1997). (Pubitemid 28016354)
46. Davies SJ, Goucher DR, Doller C, Silver J. Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J. Neurosci. 19(14), 5810-5822 (1999). (Pubitemid 29327918)
47. Cai D, Deng K, Mellado W, Lee J, Ratan RR, Filbin MT. Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron 35(4), 711-719 (2002).
48. Schmidt S, Haase CG, Bezman L et al. Serum autoantibody responses to myelin oligodendrocyte glycoprotein and myelin basic protein in X-linked adrenoleukodystrophy and multiple sclerosis. J. Neuroimmunol. 119(1), 88-94 (2001). (Pubitemid 32781732)
49. Karni A, Bakimer-Kleiner R, Abramsky O, Ben-Nun A. Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis. Arch. Neurol. 56(3), 311-315 (1999). Important study that demonstrated that elevated presence of antimyelin oligodendrocyte glycoprotein antibody is not specific for multiple sclerosis because a similar appearance was also demonstrated in patients with other neurologic diseases of the CNS. (Pubitemid 29120228)
50. Endo T, Scott DD, Stewart SS, Kundu SK, Marcus DM. Antibodies to glycosphingolipids in patients with multiple sclerosis and SLE. J. Immunol. 132(4), 1793-1797 (1984). (Pubitemid 14168138)
51. Freedman MS, Laks J, Dotan N, Altstock RT, Dukler A, Sindic CJ. Anti-α-glucose-based glycan IgM antibodies predict relapse activity in multiple sclerosis after the first neurological event. Mult. Scler. 15(4), 422-430 (2009).
52. Schwarz M, Spector L, Gortler M et al. Serum anti-Glc(a1,4)Glc(a) antibodies as a biomarker for relapsing-remitting multiple sclerosis. J. Neurol. Sci. 244(1-2), 59-68 (2006).
53. Bornstein NM, Aronovich B, Korczyn AD, Shavit S, Michaelson DM, Chapman J. Antibodies to brain antigens following stroke. Neurology 56(4), 529-530 (2001). (Pubitemid 32172881)
54. Dambinova SA, Khounteev GA, Izykenova GA, Zavolokov IG, Ilyukhina AY, Skoromets AA. Blood test detecting autoantibodies to N-methyl-d-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke. Clin. Chem. 49(10), 1752-1762 (2003). (Pubitemid 37194244)
55. Davies AL, Hayes KC, Dekaban GA. Clinical correlates of elevated serum concentrations of cytokines and autoantibodies in patients with spinal cord injury. Arch. Phys. Med. Rehabil. 88(11), 1384-1393 (2007). (Pubitemid 47625318)
56. Hayes KC, Hull TC, Delaney GA et al. Elevated serum titers of proinflammatory cytokines and CNS autoantibodies in patients with chronic spinal cord injury. J. Neurotrauma 19(6), 753-761 (2002). (Pubitemid 34761337)
57. Stefan J, Prochazka M, Voltnerova M. Studies of immunologic reactions after brain injury. I. Antibodies against brain tissue lipids after experimental injury of the brain in rabbits. Int. Surg. 55(5), 316-321 (1971).
58. Skoda D, Kranda K, Bojar M et al. Antibody formation against b-tubulin Class 3 in response to brain trauma. Brain Res. Bull. 68(4), 213-216 (2006). (Pubitemid 41827724)
59. Ponomarenko NA, Durova OM, Vorobiev II et al. Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen. Proc. Natl Acad. Sci. USA 103(2), 281-286 (2006). Identified antibodies with catalytic properties capable of hydrolyzing MBP, arguing in favor of a pathological role for anti-MBP antibodies in multiple sclerosis. (Pubitemid 43122392)
60. Ponomarenko NA, Durova OM, Vorobiev II et al. Catalytic activity of autoantibodies toward myelin basic protein correlates with the scores on the multiple sclerosis expanded disability status scale. Immunol. Lett. 103(1), 45-50 (2006). (Pubitemid 43162945)
61. Taguchi H, Planque S, Nishiyama Y et al. Autoantibody-catalyzed hydrolysis of amyloid b peptide. J. Biol. Chem. 283(8), 4714-4722 (2008).
62. Lacroix-Desmazes S, Moreau A, Sooryanarayana et al. Catalytic activity of antibodies against factor VIII in patients with hemophilia A. Nat. Med. 5(9), 1044-1047 (1999). (Pubitemid 29439576)
63. Wootla B, Christophe OD, Mahendra A et al. Proteolytic antibodies activate factor IX in patients with acquired hemophilia. Blood 117(7), 2257-2264 (2011).
64. Wootla B, Dasgupta S, Dimitrov JD et al. Factor VIII hydrolysis mediated by anti-factor VIII autoantibodies in acquired hemophilia. J. Immunol. 180(11), 7714-7720 (2008).
65. Lacroix-Desmazes S, Bayry J, Kaveri SV et al. High levels of catalytic antibodies correlate with favorable outcome in sepsis. Proc. Natl Acad. Sci. USA 102(11), 4109-4113 (2005). First study to demonstrate a beneficial effect of the presence of catalytic antibodies in patients with sepsis. (Pubitemid 40388563)
66. Thiagarajan P, Dannenbring R, Matssura K, Tramontano A, Gololobov G, Paul S. Monoclonal antibody light chain with prothrombinase activity. Biochemistry 39, 6459-6465 (2000). (Pubitemid 30347151)
67. Wootla B, Nicoletti A, Patey N et al. Hydrolysis of coagulation factors by circulating IgG is associated with a reduced risk for chronic allograft nephropathy in renal transplanted patients. J. Immunol. 180(12), 8455-8460 (2008).
68. Wootla B, Lacroix-Desmazes S, Warrington AE, Bieber AJ, Kaveri SV, Rodriguez M. Autoantibodies with enzymatic properties in human autoimmune diseases. J. Autoimmun. 37(2), 144-150 (2011).
69. Wootla B, Denic A, Keegan BM et al. Evidence for the role of B cells and immunoglobulins in the pathogenesis of multiple sclerosis. Neurol. Res. Int. 2011, 780712 (2011).
70. Rodriguez M, Lennon VA, Benveniste EN, Merrill JE. Remyelination by oligodendrocytes stimulated by antiserum to spinal cord. J. Neuropathol. Exp. Neurol. 46(1), 84-95 (1987). (Pubitemid 17232257)
71. Howe CL, Bieber AJ, Warrington AE, Pease LR, Rodriguez M. Antiapoptotic signaling by a remyelination-promoting human antimyelin antibody. Neurobiol. Dis. 15(1), 120-131 (2004). (Pubitemid 38134387)
72. Miller DJ, Rodriguez M. A monoclonal autoantibody that promotes central nervous system remyelination in a model of multiple sclerosis is a natural autoantibody encoded by germline immunoglobulin genes. J. Immunol. 154(5), 2460-2469 (1995).
73. Warrington AE, Asakura K, Bieber AJ et al. Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis. Proc. Natl Acad. Sci. USA 97(12), 6820-6825 (2000). (Pubitemid 30412798)
74. Mitsunaga Y, Ciric B, Van Keulen V et al. Direct evidence that a human antibody derived from patient serum can promote myelin repair in a mouse model of chronic-progressive demyelinating disease. FASEB J. 16(10), 1325-1327 (2002).
75. Warrington AE, Bieber AJ, Van Keulen V, Ciric B, Pease LR, Rodriguez M. Neuron-binding human monoclonal antibodies support central nervous system neurite extension. J. Neuropathol. Exp. Neurol. 63(5), 461-473 (2004). (Pubitemid 38669667)
76. Van Keulen VP, Ciric B, Radhakrishnan S et al. Immunomodulation using the recombinant monoclonal human B7-DC cross-linking antibody rHIgM12. Clin. Exp. Immunol. 143(2), 314-321 (2006).
77. Xu X, Warrington AE, Wright BR et al. A human IgM signals axon outgrowth: Coupling lipid raft to microtubules. J. Neurochem. 119(1), 100-112 (2011).
78. Denic A, Macura SI, Warrington AE et al. A single dose of neuron-binding human monoclonal antibody improves spontaneous activity in a murine model of demyelination. PLoS One 6(10), e26001 (2011).
79. Casali P, Schettino EW. Structure and function of natural antibodies. Curr. Top Microbiol. Immunol. 210, 167-179 (1996). (Pubitemid 26024271)
80. Baumgarth N. The double life of a B-1 cell: Self-reactivity selects for protective effector functions. Nat. Rev. Immunol. 11(1), 34-46 (2011).
81. Warrington AE, Van Keulen V, Pease LR, Rodriguez M. Naturally occurring antibodies as therapeutics for neurologic disease: Can human monoclonal IgMs replace the limited resource IVIg? In:Naturally Occurring Antibodies (NAbs). Lutz HU (Ed.). Landes Bioscience and Springer Science + Business Media, NY, USA (2011).
82. Watzlawik J, Holicky E, Edberg DD et al. Human remyelination promoting antibody inhibits apoptotic signaling and differentiation through Lyn kinase in primary rat oligodendrocytes. Glia 58(15), 1782-1793 (2010).
83. Popovich PG, Longbrake EE. Can the immune system be harnessed to repair the CNS? Nat. Rev. Neurosci. 9(6), 481-493 (2008). (Pubitemid 351704948)
84. Cao Q, He Q, Wang Y et al. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury. J. Neurosci. 30(8), 2989-3001 (2010).
85. Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS study: A randomized controlled trial. Alteplase thrombolysis for acute noninterventional therapy in ischemic stroke. JAMA 282(21), 2019-2026 (1999).
86. Cudkowicz ME, Katz J, Moore DH et al. Toward more efficient clinical trials for amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 11(3), 259-265 (2010).
87. Gurney ME, Fleck TJ, Himes CS, Hall ED. Riluzole preserves motor function in a transgenic model of familial amyotrophic lateral sclerosis. Neurology 50(1), 62-66 (1998).
88. Miller RG, Mitchell JD, Lyon M, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst. Rev. 1, CD001447 (2007).
89. Coles AJ, Fox E, Vladic A et al. Alemtuzumab versus interferon β-1a in early relapsing-remitting multiple sclerosis: Post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 10(4), 338-348 (2011).
90. Fox EJ, Sullivan HC, Gazda SK et al. A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis. Eur. J. Neurol. 19(2), 307-311 (2012).
91. Bielekova B, Richert N, Herman ML et al. Intrathecal effects of daclizumab treatment of multiple sclerosis. Neurology 77(21), 1877-1886 (2011).
92. Brown BA, Torabi M. Incidence of infusion-associated reactions with rituximab for treating multiple sclerosis: A retrospective analysis of patients treated at a US centre. Drug Saf. 34(2), 117-123 (2011).
93. Mi S, Lee X, Shao Z et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat. Neurosci. 7(3), 221-228 (2004). (Pubitemid 38280445)
94. Mi S, Miller RH, Lee X et al. LINGO-1 negatively regulates myelination by oligodendrocytes. Nat. Neurosci. 8(6), 745-751 (2005). (Pubitemid 43085840)
95. Mi S, Hu B, Hahm K et al. LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis. Nat. Med. 13(10), 1228-1233 (2007). (Pubitemid 47530642)
96. Warrington AE, Bieber AJ, Ciric B, Pease LR, Van Keulen V, Rodriguez M. A recombinant human IgM promotes myelin repair after a single, very low dose. J. Neurosci. Res. 85(5), 967-976 (2007). (Pubitemid 46580338)
97. Banerjee S, Bhat MA. Neuron-glial interactions in blood-brain barrier formation. Annu. Rev. Neurosci. 30, 235-258 (2007). (Pubitemid 47218757)
98. Steinmetz MP, Horn KP, Tom VJ et al. Chronic enhancement of the intrinsic growth capacity of sensory neurons combined with the degradation of inhibitory proteoglycans allows functional regeneration of sensory axons through the dorsal root entry zone in the mammalian spinal cord. J. Neurosci. 25(35), 8066-8076 (2005). (Pubitemid 41254410)
99. Barritt AW, Davies M, Marchand F et al. Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J. Neurosci. 26(42), 10856-10867 (2006).
100. Santoro SW, Joyce GF. A general purpose RNA-cleaving DNA enzyme. Proc. Natl Acad. Sci. USA 94(9), 4262-4266 (1997). (Pubitemid 27194229)
101. Grimpe B, Silver J. A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord. J. Neurosci. 24(6), 1393-1397 (2004). (Pubitemid 38222990)
102. Park KK, Liu K, Hu Y et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322(5903), 963-966 (2008).
103. McDonald JW, Liu XZ, Qu Y et al. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat. Med. 5(12), 1410-1412 (1999).
104. Toda H, Takahashi J, Iwakami N et al. Grafting neural stem cells improved the impaired spatial recognition in ischemic rats. Neurosci. Lett. 316(1), 9-12 (2001). (Pubitemid 33092021)
105. Chen J, Li Y, Wang L et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32(4), 1005-1011 (2001). (Pubitemid 32285175)
106. Munoz-Elias G, Marcus AJ, Coyne TM, Woodbury D, Black IB. Adult bone marrow stromal cells in the embryonic brain: Engraftment, migration, differentiation, and long-term survival. J. Neurosci. 24(19), 4585-4595 (2004). (Pubitemid 38656614)
107. Sykova E, Homola A, Mazanec R et al. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant. 15(8-9), 675-687 (2006). (Pubitemid 46095251)
108. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat. Med. 8(9), 963-970 (2002). (Pubitemid 35033700)
109. Ming GL, Song H. Adult neurogenesis in the mammalian central nervous system. Annu. Rev. Neurosci. 28, 223-250 (2005). (Pubitemid 41098905)
110. Verdu E, Garcia-Alias G, Fores J, Lopez-Vales R, Navarro X. Olfactory ensheathing cells transplanted in lesioned spinal cord prevent loss of spinal cord parenchyma and promote functional recovery. Glia 42(3), 275-286 (2003). (Pubitemid 36538340)
111. Kawada H, Takizawa S, Takanashi T et al. Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation 113(5), 701-710 (2006).
112. Erdo F, Buhrle C, Blunk J et al. Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke. J. Cereb. Blood Flow Metab. 23(7), 780-785 (2003). (Pubitemid 36818686)
113. Case LC, Tessier-Lavigne M. Regeneration of the adult central nervous system. Curr. Biol. 15(18), R749-R753 (2005).
114. Souan ML, Geffard M, Vieillemaringe J, Lebrun-Grandie P, Orgogozo JM. Anti-acetylcholine antibodies and the pathogenesis of myasthenia gravis. Ann. NY Acad. Sci. 505, 423-438 (1987).
115. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J. Exp. Med. 202(4), 473-477 (2005). (Pubitemid 41186945)
116. Motomura M, Lang B, Johnston I, Palace J, Vincent A, Newsom-Davis J. Incidence of serum anti-P/O-type and anti-N-type calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. J. Neurol. Sci. 147(1), 35-42 (1997). (Pubitemid 27117502)
117. Stich O, Klages E, Bischler P et al. SOX1 antibodies in sera from patients with paraneoplastic neurological syndromes. Acta Neurol. Scand. (2011).
118. Lardone RD, Yuki N, Odaka M, Daniotti JL, Irazoqui FJ, Nores GA. Anti-GM1 IgG antibodies in Guillain-Barre syndrome: Fine specificity is associated with disease severity. J. Neurol. Neurosurg. Psychiatry 81(6), 629-633 (2010).
119. Pittock SJ, Lucchinetti CF, Lennon VA. Anti-neuronal nuclear autoantibody Type 2: Paraneoplastic accompaniments. Ann. Neurol. 53(5), 580-587 (2003). (Pubitemid 36529431)
120. Hoffmann LA, Jarius S, Pellkofer HL et al. Anti-Ma and anti-Ta associated paraneoplastic neurological syndromes: 22 newly diagnosed patients and review of previous cases. J. Neurol. Neurosurg. Psychiatry 79(7), 767-773 (2008). (Pubitemid 351914721)
121. Dalmau J, Graus F, Villarejo A et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 127(Pt 8), 1831-1844 (2004). (Pubitemid 39061559)
122. Pittock SJ, Lucchinetti CF, Parisi JE et al. Amphiphysin autoimmunity: Paraneoplastic accompaniments. Ann. Neurol. 58(1), 96-107 (2005). (Pubitemid 40962465)
123. Graus F, Dalmau J, Valldeoriola F et al. Immunological characterization of a neuronal antibody (anti-Tr) associated with paraneoplastic cerebellar degeneration and Hodgkin's disease. J. Neuroimmunol. 74(1-2), 55-61 (1997). (Pubitemid 27128977)
124. Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 42(10), 1931-1937 (1992).
125. Graus F, Keime-Guibert F, Rene R et al. Anti-Hu-associated paraneoplastic encephalomyelitis: Analysis of 200 patients. Brain 124(Pt 6), 1138-1148 (2001). (Pubitemid 32510382)
126. Adamus G, Guy J, Schmied JL, Arendt A, Hargrave PA. Role of anti-recoverin autoantibodies in cancer-associated retinopathy. Invest. Ophthalmol. Vis. Sci. 34(9), 2626-2633 (1993). (Pubitemid 23232470)
127. Shiraga S, Adamus G. Mechanism of CAR syndrome: Anti-recoverin antibodies are the inducers of retinal cell apoptotic death via the caspase 9- and caspase 3-dependent pathway. J. Neuroimmunol. 132(1-2), 72-82 (2002). (Pubitemid 35333328)
128. Honnorat J, Antoine JC, Derrington E, Aguera M, Belin MF. Antibodies to a subpopulation of glial cells and a 66 kDa developmental protein in patients with paraneoplastic neurological syndromes. J. Neurol. Neurosurg. Psychiatry 61(3), 270-278 (1996). (Pubitemid 26293722)
129. Eisenbarth GS, Walsh FS, Nirenberg M. Monoclonal antibody to a plasma membrane antigen of neurons. Proc. Natl Acad. Sci. USA 76(10), 4913-4917 (1979). (Pubitemid 10229095)
130. Inoko E, Nishiura Y, Tanaka H et al. Developmental stage-dependent expression of an a2,8-trisialic acid unit on glycoproteins in mouse brain. Glycobiology 20(7), 916-928 (2010).
131. Bansal R, Warrington AE, Gard AL, Ranscht B, Pfeiffer SE. Multiple and novel specificities of monoclonal antibodies O1, O4, and R-mAb used in the analysis of oligodendrocyte development. J. Neurosci. Res. 24(4), 548-557 (1989). (Pubitemid 20015347)