Neuroinflammation in spinal cord injury: therapeutic targets for neuroprotection and regeneration

Progress in Brain Research

Volumn 175, Issue , 2009, Pages 125-137

  Alexander, Jessica K ^a   Popovich, Phillip G ^b  

^a THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

^b Center for Brain and Spinal Cord Repair   (United States)

Author keywords

inflammation; macrophage; microglia; neuroinflammation; regeneration; spinal cord injury

Indexed keywords

4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; CYCLOSPORIN A; CYTOKINE; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GROWTH FACTOR; INFLIXIMAB; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 1BETA; INTERLEUKIN 4; METHOTREXATE; METHYLPREDNISOLONE; MINOCYCLINE; PROTEINASE; TACROLIMUS; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA;

CELL TRANSPLANTATION; CELLULAR IMMUNITY; CONVALESCENCE; DISEASE EXACERBATION; GLIA; HUMAN; INFLAMMATION; MACROPHAGE ACTIVATION; MICROENVIRONMENT; MICROGLIA; NERVE CELL LESION; NERVE CELL NECROSIS; NERVE CELL PLASTICITY; NERVE GROWTH; NERVE REGENERATION; NEUROPROTECTION; NONHUMAN; PAIN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SINGLE DRUG DOSE; SPINAL CORD INJURY;

ANIMALS; HUMANS; INFLAMMATION; NERVE REGENERATION; NEUROPROTECTIVE AGENTS; SPINAL CORD INJURIES;

EID: 68049098298     PISSN: 00796123     EISSN: None     Source Type: Book Series    
DOI: 10.1016/S0079-6123(09)17508-8     Document Type: Review

References (168)

1. Aarabi B., Hesdorffer D.C., Ahn E.S., Aresco C., Scalea T.M., and Eisenberg H.M. Outcome following decompressive craniectomy for malignant swelling due to severe head injury. Journal of Neurosurgery 104 (2006) 469-479
2. Agrawal S.K., and Fehlings M.G. Role of NMDA and non-NMDA ionotropic glutamate receptors in traumatic spinal cord axonal injury. Journal of Neuroscience 17 (1997) 1055-1063
3. Ankeny D.P., Lucin K.M., Sanders V.M., McGaughy V.M., and Popovich P.G. Spinal cord injury triggers systemic autoimmunity: evidence for chronic B lymphocyte activation and lupus-like autoantibody synthesis. Journal of Neurochemistry 99 (2006) 1073-1087
4. Ankeny D.P., and Popovich P.G. Mechanisms and implications of adaptive immune responses after traumatic spinal cord injury. Neuroscience 158 3 (2009) 1112-1121
5. Anthony D.C., Blond D., Dempster R., and Perry V.H. Chemokine targets in acute brain injury and disease. Progress in Brain Research 132 (2001) 507-524
6. Armao D., Kornfeld M., Estrada E.Y., Grossetete M., and Rosenberg G.A. Neutral proteases and disruption of the blood-brain barrier in rat. Brain Research 767 (1997) 259-264
7. Assina R., Sankar T., Theodore N., Javedan S.P., Gibson A.R., Horn K.M., et al. Activated autologous macrophage implantation in a large-animal model of spinal cord injury. Neurosurgical Focus 25 (2008) E3
8. Bao F., Chen Y., Dekaban G.A., and Weaver L.C. An anti-CD11d integrin antibody reduces cyclooxygenase-2 expression and protein and DNA oxidation after spinal cord injury in rats. Journal of Neurochemistry 90 (2004) 1194-1204
9. Baptiste D.C., and Fehlings M.G. Update on the treatment of spinal cord injury. Progress in Brain Research 161 (2007) 217-233
10. Baptiste D.C., Hartwick A.T., Jollimore C.A., Baldridge W.H., Seigel G.M., and Kelly M.E. An investigation of the neuroprotective effects of tetracycline deritvaives in experimental models of retinal cell death. Molecular Pharmacology 66 (2004) 1113-1122
11. Barrette B., Hebert M.A., Filali M., Lafortune K., Vallieres N., Gowing G., et al. Requirement of myeloid cells for axon regeneration. Journal of Neuroscience 28 (2008) 9363-9376
12. Bartholdi D., and Schwab M.E. Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: an in situ hybridization study. European Journal of Neuroscience 9 (1997) 1422-1438
13. Bessis A., Bechade C., Bernard D., and Roumier A. Microglial control of neuronal death and synaptic properties. Glia 55 (2007) 233-238
14. Birdsall Abrams M., Josephson A., Dominguez C., Oberg J., Diez M., Spenger C., et al. Recovery from spinal cord injury differs between rat strains in a major histocompatibility complex-independent manner. European Journal of Neuroscience 26 (2007) 1118-1127
15. Blight A.R. Effects of silica on the outcome from experimental spinal cord injury: implication of macrophages in secondary tissue damage. Neuroscience 60 (1994) 263-273
16. Boivin A., Pineau I., Barrette B., Filali M., Vallieres N., Rivest S., et al. Toll-like receptor signaling is critical for Wallerian degeneration and functional recovery after peripheral nerve injury. Journal of Neuroscience 27 (2007) 12565-12576
17. Bowman C.C., Rasley A., Tranguch S.L., and Marriott I. Cultured astrocytes express toll-like receptors for bacterial products. Glia 43 (2003) 281-291
18. Bracken M.B., Shepard M.J., Collins Jr. W.F., Holford T.R., Baskin D.S., Eisenberg H.M., et al. Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the Second National Acute Spinal Cord Injury Study. Journal of Neurosurgery 76 (1992) 23-31
19. Bracken M.B., Shepard M.J., Holford T.R., Leo-Summers L., Aldrich E.F., Fazl M., et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 277 (1997) 1597-1604
20. Brambilla R., Bracchi-Ricard V., Hu W.H., Frydel B., Bramwell A., Karmally S., et al. Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. Journal of Experimental Medicine 202 (2005) 145-156
21. Bush T.G., Puvanachandra N., Horner C.H., Polito A., Ostenfeld T., Svendsen C.N., et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23 (1999) 297-308
22. Campbell S.J., Perry V.H., Pitossi F.J., Butchart A.G., Chertoff M., Waters S., et al. Central nervous system injury triggers hepatic CC and CXC chemokine expression that is associated with leukocyte mobilization and recruitment to both the central nervous system and the liver. American Journal of Pathology 166 (2005) 1487-1497
23. Cardona A.E., Li M., Liu L., Savarin C., and Ransohoff R.M. Chemokines in and out of the central nervous system: much more than chemotaxis and inflammation. Journal of Leukocyte Biolology 84 (2008) 587-594
24. Carlson S.L., Parrish M.E., Springer J.E., Doty K., and Dossett L. Acute inflammatory response in spinal cord following impact injury. Experimental Neurology 151 (1998) 77-88
25. Chang H.T. Subacute human spinal cord contusion: few lymphocytes and many macrophages. Spinal Cord 45 (2007) 174-182
26. Chen Q., Smith G.M., and Shine H.D. Immune activation is required for NT-3-induced axonal plasticity in chronic spinal cord injury. Experimental Neurology 209 (2008) 497-509
27. Coull J.A., Beggs S., Boudreau D., Boivin D., Tsuda M., Inoue K., et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438 (2005) 1017-1021
28. Crown E.D., Gwak Y.S., Ye Z., Johnson K.M., and Hulsebosch C.E. Activation of p38 MAP kinase is involved in central neuropathic pain following spinal cord injury. Experimental Neurology 213 (2008) 257-267
29. Davalos D., Grutzendler J., Yang G., Kim J.V., Zuo Y., Jung S., et al. ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 8 (2005) 752-758
30. Davies A.L., Hayes K.C., and Dekaban G.A. Clinical correlates of elevated serum concentrations of cytokines and autoantibodies in patients with spinal cord injury. Archives of Physical Medicine and Rehabilitation 88 (2007) 1384-1393
31. DeLeo J.A., and Yezierski R.P. The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 90 (2001) 1-6
32. Detloff M.R., Fisher L.C., McGaughy V., Longbrake E.E., Popovich P.G., and Basso D.M. Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats. Experimental Neurology 212 (2008) 337-347
33. Donnelly D.J., and Popovich P.G. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Experimental Neurology 209 (2008) 378-388
34. Elkabes S., DiCicco-Bloom E.M., and Black I.B. Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. Journal of Neuroscience 16 (1996) 2508-2521
35. Engelhardt B., and Ransohoff R.M. The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends in Immunology 26 (2005) 485-495
36. Faden A.I., and Simon R.P. A potential role for excitotoxins in the pathophysiology of spinal cord injury. Annals of Neurology 23 (1988) 623-626
37. Farooque M., Isaksson J., and Olsson Y. Improved recovery after spinal cord trauma in ICAM-1 and P-selectin knockout mice. Neuroreport 10 (1999) 131-134
38. Farooque M., Isaksson J., and Olsson Y. White matter preservation after spinal cord injury in ICAM-1/P-selectin-deficient mice. Acta Neuropathologica 102 (2001) 132-140
39. Faulkner J.R., Herrmann J.E., Woo M.J., Tansey K.E., Doan N.B., and Sofroniew M.V. Reactive astrocytes protect tissue and preserve function after spinal cord injury. Journal of Neuroscience 24 (2004) 2143-2155
40. Fehlings M.G., Tator C.H., and Linden R.D. The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow. Electroencephalography and Clinical Neurophysiology 74 (1989) 241-259
41. Festoff B.W., Ameenuddin S., Arnold P.M., Wong A., Santacruz K.S., and Citron B.A. Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury. Journal of Neurochemistry 97 (2006) 1314-1326
42. Fleming J.C., Norenberg M.D., Ramsay D.A., Dekaban G.A., Marcillo A.E., Saenz A.D., et al. The cellular inflammatory response in human spinal cords after injury. Brain 129 (2006) 3249-3269
43. Gensel J.C., Nakamura S., Guan Z., van Rooijen N., Ankeny D.P., and Popovich P.G. Macrophages promote axon regeneration with concurrent neurotoxicity. Journal of Neuroscience 29 12 (2009) 3956-3968
44. Ghirnikar R.S., Lee Y.L., and Eng L.F. Chemokine antagonist infusion attenuates cellular infiltration following spinal cord contusion injury in rat. Journal of Neuroscience Research 59 (2000) 63-73
45. Ghirnikar R.S., Lee Y.L., and Eng L.F. Chemokine antagonist infusion promotes axonal sparing after spinal cord contusion injury in rat. Journal of Neuroscience Research 64 (2001) 582-589
46. Giulian D., and Robertson C. Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Annals of Neurology 27 (1990) 33-42
47. Glaser J., Gonzalez R., Sadr E., and Keirstead H.S. Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injury. Journal of Neuroscience Research 84 (2006) 724-734
48. Gonzalez R., Glaser J., Liu M.T., Lane T.E., and Keirstead H.S. Reducing inflammation decreases secondary degeneration and functional deficit after spinal cord injury. Experimental Neurology 184 (2003) 456-463
49. Gonzalez R., Hickey M.J., Espinosa J.M., Nistor G., Lane T.E., and Keirstead H.S. Therapeutic neutralization of CXCL10 decreases secondary degeneration and functional deficit after spinal cord injury in mice. Regenerative Medicine 2 (2007) 771-783
50. Gordon S. Alternative activation of macrophages. Nature Reviews Immunology 3 (2003) 23-35
51. Gris D., Marsh D.R., Oatway M.A., Chen Y., Hamilton E.F., Dekaban G.A., et al. Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. Journal of Neuroscience 24 (2004) 4043-4051
52. Guo G., and Bhat N.R. p38alpha MAP kinase mediates hypoxia-induced motor neuron cell death: a potential target of minocycline's neuroprotective action. Neurochemical Research 32 (2007) 2160-2166
53. Guo W., Wang H., Watanabe M., Shimizu K., Zou S., LaGraize S.C., et al. Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain. Journal of Neuroscience 27 (2007) 6006-6018
54. Guzmán-Lenis M.S., Vallejo C., Navarro X., and Casas C. Analysis of FK506-mediated protection in an organotypic model of spinal cord damage: heat shock protein 70 levels are modulated in microglial cells. Neuroscience 155 (2008) 104-113
55. Haddad, E., McAlister, V., Renouf, E., Malthaner, R., Kjaer, M. S., & Gluud, L. L. (2006). Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database of Systematic Reviews, Issue 4, Art. No. CD005161 (DOI:10.1002/14651858.CD005161.pub2).
56. Hains B.C., and Waxman S.G. Activated microglia contribute to the maintenance of chronic pain after spinal cord injury. Journal of Neuroscience 26 (2006) 4308-4317
57. Hamada Y., Ikata T., Katoh S., Nakauchi K., Niwa M., Kawai Y., et al. Involvement of an intercellular adhesion molecule 1-dependent pathway in the pathogenesis of secondary changes after spinal cord injury in rats. Journal of Neurochemistry 66 (1996) 1525-1531
58. Hamamoto Y., Ogata T., Morino T., Hino M., and Yamamoto H. Real-time direct measurement of spinal cord blood flow at the site of compression: relationship between blood flow recovery and motor deficiency in spinal cord injury. Spine 32 (2007) 1955-1962
59. Hashizume H., Rutkowski M.D., Weinstein J.N., and DeLeo J.A. Central administration of methotrexate reduces mechanical allodynia in an animal model of radiculopathy/sciatica. Pain 87 (2000) 159-169
60. Hayashi Y., Shumsky J.S., Connors T., Otsuka T., Fischer I., Tessler A., et al. Immunosuppression with either cyclosporine a or FK506 supports survival of transplanted fibroblasts and promotes growth of host axons into the transplant after spinal cord injury. Journal of Neurotrauma 22 (2005) 1267-1281
61. Henry C.J., Huang Y., Wynne A., Hanke M., Himler J., Bailey M.T., et al. Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. Journal of Neuroinflammation 5 (2008) 15
62. Henson P.M., Bratton D.L., and Fadok V.A. The phosphatidylserine receptor: a crucial molecular switch?. Nature Reviews Molecular Cell Biology 2 (2001) 627-633
63. Horiuchi H., Ogata T., Morino T., Chuai M., and Yamamoto H. Continuous intrathecal infusion of SB203580, a selective inhibitor of p38 mitogen-activated protein kinase, reduces the damage of hind-limb function after thoracic spinal cord injury in rat. Neuroscience Research 47 (2003) 209-217
64. Horn K.P., Busch S.A., Hawthorne A.L., van Rooijen N., and Silver J. Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. Journal of Neuroscience 28 (2008) 9330-9341
65. Hua F., Ma J., Ha T., Kelley J., Williams D.L., Kao R.L., et al. Preconditioning with a TLR2 specific ligand increases resistance to cerebral ischemia/reperfusion injury. Journal of Neuroimmunology 199 (2008) 75-82
66. Hua F., Ma J., Ha T., Xia Y., Kelley J., Williams D.L., et al. Activation of toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. Journal of Neuroimmunology 190 (2007) 101-111
67. Hugenholtz H. Methylprednisolone for acute spinal cord injury: not a standard of care. CMAJ 168 (2003) 1145-1146
68. Hurlbert R.J., and Hamilton M.G. Methylprednisolone for acute spinal cord injury: 5-year practice reversal. Canadian Journal of Neurological Science 35 (2008) 41-45
69. Hutchinson M.R., Bland S.T., Johnson K.W., Rice K.C., Maier S.F., and Watkins L.R. Opioid-induced glial activation: mechanisms of activation and implications for opioid analgesia, dependence, and reward. ScientificWorld Journal 7 (2007) 98-111
70. Ibarra A., and Diaz-Ruiz A. Protective effect of cyclosporin-A in spinal cord injury: an overview. Current Medicinal Chemistry 13 (2006) 2703-2710
71. James S.E., Burden H., Burgess R., Xie Y., Yang T., Massa S.M., et al. Anti-cancer drug induced neurotoxicity and identification of Rho pathway signaling modulators as potential neuroprotectants. Neurotoxicology 29 (2008) 605-612
72. Jones T.B., Hart R.P., and Popovich P.G. Molecular control of physiological and pathological T-cell recruitment after mouse spinal cord injury. Journal of Neuroscience 25 (2005) 6576-6583
73. Kaminska B., Gaweda-Walerych K., and Zawadzka M. Molecular mechanisms of neuroprotective action of immunosuppressants-facts and hypotheses. Journal of Cellular and Molecular Medicine 8 (2004) 45-58
74. Kaymaz M., Emmez H., Bukan N., Dursun A., Kurt G., Pasaoglu H., et al. Effectiveness of FK506 on lipid peroxidation in the spinal cord following experimental traumatic injury. Spinal Cord 43 (2005) 22-26
75. Kigerl K.A., Lai W., Rivest S., Hart R.P., Satoskar A.R., and Popovich P.G. Toll-like receptor (TLR)-2 and TLR-4 regulate inflammation, gliosis, and myelin sparing after spinal cord injury. Journal of Neurochemistry 102 (2007) 37-50
76. Kigerl K.A., McGaughy V.M., and Popovich P.G. Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury. Journal of Comparative Neurology 494 (2006) 578-594
77. Kim D., Kim M.A., Cho I.H., Kim M.S., Lee S., Jo E.K., et al. A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. Journal of Biological Chemistry 282 (2007) 14975-14983
78. Kim G.M., Xu J., Xu J., Song S.K., Yan P., Ku G., et al. Tumor necrosis factor receptor deletion reduces nuclear factor-kappaB activation, cellular inhibitor of apoptosis protein 2 expression, and functional recovery after traumatic spinal cord injury. Journal of Neuroscience 21 (2001) 6617-6625
79. Koizumi S., Shigemoto-Mogami Y., Nasu-Tada K., Shinozaki Y., Ohsawa K., Tsuda M., et al. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446 (2007) 1091-1095
80. Kostyk S.K., Popovich P.G., Stokes B.T., Wei P., and Jakeman L.B. Robust axonal growth and a blunted macrophage response are associated with impaired functional recovery after spinal cord injury in the MRL/MpJ mouse. Neuroscience 156 (2008) 498-514
81. Koyanagi I., Iwasaki Y., Isu T., Akino M., and Abe H. Significance of spinal cord swelling in the prognosis of acute cervical spinal cord injury. Paraplegia 27 (1989) 190-197
82. Kurt G., Ergun E., Cemil B., Borcek A.O., Borcek P., Gulbahar O., et al. Neuroprotective effects of infliximab in experimental spinal cord injury. Surgical Neurology 71 3 (2009) 332-336
83. Lazarov-Spiegler O., Solomon A.S., and Schwartz M. Peripheral nerve-stimulated macrophages simulate a peripheral nerve-like regenerative response in rat transected optic nerve. Glia 24 (1998) 329-337
84. Lazarov-Spiegler O., Solomon A.S., Zeev-Brann A.B., Hirschberg D.L., Lavie V., and Schwartz M. Transplantation of activated macrophages overcomes central nervous system regrowth failure. FASEB Journal 10 (1996) 1296-1302
85. Lee H.C., Cho D.Y., Lee W.Y., and Chuang H.C. Pitfalls in treatment of acute cervical spinal cord injury using high-dose methylprednisolone: a retrospect audit of 111 patients. Surgical Neurology 68 Suppl. 1 (2007) S37-S41 discussion S41-42
86. Lee M., Lee E.S., Kim Y.S., Choi B.H., Park S.R., Park H.S., et al. Ischemic injury-specific gene expression in the rat spinal cord injury model using hypoxia-inducible system. Spine 30 (2005) 2729-2734
87. Lee J.M., Yan P., Xiao Q., Chen S., Lee K.Y., Hsu C.Y., et al. Methylprednisolone protects oligodendrocytes but not neurons after spinal cord injury. Journal of Neuroscience 28 (2008) 3141-3149
88. Lee Y.B., Yune T.Y., Baik S.Y., Shin Y.H., Du S., Rhim H., et al. Role of tumor necrosis factor-alpha in neuronal and glial apoptosis after spinal cord injury. Experimental Neurology 166 (2000) 190-195
89. Lee S.M., Yune T.Y., Kim S.J., Park D.W., Lee Y.K., Kim Y.C., et al. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. Journal of Neurotrauma 20 (2003) 1017-1027
90. Lehnardt S., Schott E., Trimbuch T., Laubisch D., Krueger C., Wulczyn G., et al. A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS. Journal of Neuroscience 28 (2008) 2320-2331
91. Leon S., Yin Y., Nguyen J., Irwin N., and Benowitz L.I. Lens injury stimulates axon regeneration in the mature rat optic nerve. Journal of Neuroscience 20 (2000) 4615-4626
92. Liang D., Bhatta S., Gerzanich V., and Simard J.M. Cytotoxic edema: mechanisms of pathological cell swelling. Neurosurgical Focus 22 (2007) E2
93. Liu S.Q., Ma Y.G., Peng H., and Fan L. Monocyte chemoattractant protein-1 level in serum of patients with acute spinal cord injury. Chinese Journal of Traumatology 8 (2005) 216-219
94. López-Vales R., Forés J., Navarro X., and Verdú E. Olfactory ensheathing glia graft in combination with FK506 administration promote repair after spinal cord injury. Neurobiology of Disease 24 (2006) 443-454
95. López-Vales R., Garcia-Alias G., Fores J., Udina E., Gold B.G., Navarro X., et al. FK 506 reduces tissue damage and prevents functional deficit after spinal cord injury in the rat. Journal of Neuroscience Research 81 (2005) 827-836
96. Ma M., Wei P., Wei T., Ransohoff R.M., and Jakeman L.B. Enhanced axonal growth into a spinal cord contusion injury site in a strain of mouse (129×1/SvJ) with a diminished inflammatory response. Journal of Comparative Neurology 474 (2004) 469-486
97. Mabon P.J., Weaver L.C., and Dekaban G.A. Inhibition of monocyte/macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment. Experimental Neurology 166 (2000) 52-64
98. Marchand F., Tsantoulas C., Singh D., Grist J., Clark A.K., Bradbury E.J., et al. Effects of etanercept and minocycline in a rat model of spinal cord injury. European Journal of Pain 12 (2008) in press, doi:10.1016/j.ejpain.2008.08.001.
99. Marta M., Andersson A., Isaksson M., Kampe O., and Lobell A. Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis. European Journal of Immunology 38 (2008) 565-575
100. Mason J.L., Suzuki K., Chaplin D.D., and Matsushima G.K. Interleukin-1beta promotes repair of the CNS. Journal of Neuroscience 21 (2001) 7046-7052
101. Matzinger P. The danger model: a renewed sense of self. Science 296 (2002) 301-305
102. McTigue D.M., Tani M., Krivacic K., Chernosky A., Kelner G.S., Maciejewski D., et al. Selective chemokine mRNA accumulation in the rat spinal cord after contusion injury. Journal of Neuroscience Research 53 (1998) 368-376
103. Meagher L.C., Savill J.S., Baker A., Fuller R.W., and Haslett C. Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane B2. Journal of Leukocyte Biology 52 (1992) 269-273
104. Means E.D., and Anderson D.K. Neuronophagia by leukocytes in experimental spinal cord injury. Journal of Neuropathology and Experimental Neurology 42 (1983) 707-719
105. Myer D.J., Gurkoff G.G., Lee S.M., Hovda D.A., and Sofroniew M.V. Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129 (2006) 2761-2772
106. Nagy Z., Kolev K., Csonka E., Vastag M., and Machovich R. Perturbation of the integrity of the blood-brain barrier by fibrinolytic enzymes. Blood Coagulation and Fibrinolysis 9 (1998) 471-478
107. Nathan C. Neutrophils and immunity: challenges and opportunities. Nature Reviews Immunology 6 (2006) 173-182
108. Nesic O., Xu G.Y., McAdoo D., High K.W., Hulsebosch C., and Perez-Pol R. IL-1 receptor antagonist prevents apoptosis and caspase-3 activation after spinal cord injury. Journal of Neurotrauma 18 (2001) 947-956
109. Nguyen H.X., Galvan M.D., and Anderson A.J. Characterization of early and terminal complement proteins associated with polymorphonuclear leukocytes in vitro and in vivo after spinal cord injury. Journal of Neuroinflammation 5 (2008) 26
110. Noble L.J., Donovan F., Igarashi T., Goussev S., and Werb Z. Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events. Journal of Neuroscience 22 (2002) 7526-7535
111. Nottingham S., Knapp P., and Springer J. FK506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury. Experimental Neurology 177 (2002) 242-251
112. O'Carroll S.J., Alkadhi M., Nicholson L.F., and Green C.R. Connexin 43 mimetic peptides reduce swelling, astrogliosis, and neuronal cell death after spinal cord injury. Cell Communication and Adhesion 15 (2008) 27-42
113. Okada S., Nakamura M., Katoh H., Miyao T., Shimazaki T., Ishii K., et al. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nature Medicine 12 (2006) 829-834
114. Pender M.P., and Rist M.J. Apoptosis of inflammatory cells in immune control of the nervous system: role of glia. Glia 36 (2001) 137-144
115. Perrin F.E., Lacroix S., Aviles-Trigueros M., and David S. Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha and interleukin-1beta in Wallerian degeneration. Brain 128 (2005) 854-866
116. Persson M., Brantefjord M., Hansson E., and Ronnback L. Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-alpha. Glia 51 (2005) 111-120
117. Pineau I., and Lacroix S. Endogenous signals initiating inflammation in the injured nervous system. Glia 57 (2008) 351-361
118. Pinzon A., Marcillo A., Quintana A., Stamler S., Bunge M.B., Bramlett H.M., et al. A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model. Brain Research 1243 (2008) 146-151
119. Pointillart V., Petitjean M.E., Wiart L., Vital J.M., Lassie P., Thicoipe M., et al. Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 38 (2000) 71-76
120. Popovich P.G., Guan Z., McGaughy V., Fisher L., Hickey W.F., and Basso D.M. The neuropathological and behavioral consequences of intraspinal microglial/macrophage activation. Journal of Neuropathology and Experimental Neurology 61 (2002) 623-633
121. Popovich P.G., Guan Z., Wei P., Huitinga I., van Rooijen N., and Stokes B.T. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Experimental Neurology 158 (1999) 351-365
122. Popovich P.G., and Longbrake E.E. Can the immune system be harnessed to repair the CNS?. Nature Reviews Neuroscience 9 (2008) 481-493
123. Popovich P.G., van Rooijen N., Hickey W.F., Preidis G., and McGaughy V. Hematogenous macrophages express CD8 and distribute to regions of lesion cavitation after spinal cord injury. Experimental Neurology 182 (2003) 275-287
124. Popovich P.G., Wei P., and Stokes B.T. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. Journal of Comparative Neurology 377 (1997) 443-464
125. Rabchevsky A.G., Fugaccia I., Sullivan P.G., and Scheff S.W. Cyclosporin A treatment following spinal cord injury to the rat: behavioral effects and stereological assessment of tissue sparing. Journal of Neurotrauma 18 (2001) 513-522
126. Ranganathan P. An update on methotrexate pharmacogenetics in rheumatoid arthritis. Pharmacogenomics 9 (2008) 439-451
127. Rapalino O., Lazarov-Spiegler O., Agranov E., Velan G.J., Yoles E., Fraidakis M., et al. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nature Medicine 4 (1998) 814-821
128. Rice T., Larsen J., Rivest S., and Yong V.W. Characterization of the early neuroinflammation after spinal cord injury in mice. Journal of Neuropathology and Experimental Neurology 66 (2007) 184-195
129. Ritz M.F., and Hausmann O.N. Effect of 17beta-estradiol on functional outcome, release of cytokines, astrocyte reactivity and inflammatory spreading after spinal cord injury in male rats. Brain Research 1203 (2008) 177-188
130. Saadoun S., Bell B.A., Verkman A.S., and Papadopoulos M.C. Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. Brain 131 (2008) 1087-1098
131. Savill J.S., Wyllie A.H., Henson J.E., Walport M.J., Henson P.M., and Haslett C. Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. Journal of Clinical Investigation 83 (1989) 865-875
132. Sayer F.T., Kronvall E., and Nilsson O.G. Methylprednisolone treatment in acute spinal cord injury: the myth challenged through a structured analysis of published literature. Spine Journal 6 (2006) 335-343
133. Schaefer L., Babelova A., Kiss E., Hausser H.J., Baliova M., Krzyzankova M., et al. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. Journal of Clinical Investigation 115 (2005) 2223-2233
134. Scholz J., Abele A., Marian C., Haussler A., Herbert T.A., Woolf C.J., et al. Low-dose methotrexate reduces peripheral nerve injury-evoked spinal microglial activation and neuropathic pain behavior in rats. Pain 138 (2008) 130-142
135. Scholz M., Cinatl J., Schadel-Hopfner M., and Windolf J. Neutrophils and the blood-brain barrier dysfunction after trauma. Medicinal Research Reviews 27 (2007) 401-416
136. Schonberg D.L., Popovich P.G., and McTigue D.M. Oligodendrocyte generation is differentially influenced by toll-like receptor (TLR) 2 and TLR4-mediated intraspinal macrophage activation. Journal of Neuropathology and Experimental Neurology 66 (2007) 1124-1135
137. Schwartz M., and Yoles E. Immune-based therapy for spinal cord repair: autologous macrophages and beyond. Journal of Neurotrauma 23 (2006) 360-370
138. Sekhon L.H., and Fehlings M.G. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 26 (2001) S2-S12
139. Short D.J., El Masry W.S., and Jones P.W. High dose methylprednisolone in the management of acute spinal cord injury-a systematic review from a clinical perspective. Spinal Cord 38 (2000) 273-286
140. Simard J.M., Tsymbalyuk O., Ivanov A., Ivanova S., Bhatta S., Geng Z., et al. Endothelial sulfonylurea receptor 1-regulated NC Ca-ATP channels mediate progressive hemorrhagic necrosis following spinal cord injury. Journal of Clinical Investigation 117 (2007) 2105-2113
141. Sosa I., Reyes O., and Kuffler D.P. Immunosuppressants: neuroprotection and promoting neurological recovery following peripheral nerve and spinal cord lesions. Experimental Neurology 195 (2005) 7-15
142. Sroga J.M., Jones T.B., Kigerl K.A., McGaughy V.M., and Popovich P.G. Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. Journal of Comparative Neurology 462 (2003) 223-240
143. Stirling D.P., Khodarahmi K., Liu J., McPhail L.T., McBride C.B., Steeves J.D., et al. Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury. Journal of Neuroscience 24 (2004) 2182-2190
144. Stirling D.P., and Yong V.W. Dynamics of the inflammatory response after murine spinal cord injury revealed by flow cytometry. Journal of Neuroscience Research 86 (2008) 1944-1958
145. Stout R.D., Jiang C., Matta B., Tietzel I., Watkins S.K., and Suttles J. Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. Journal of Immunology 175 (2005) 342-349
146. Suberviola B., Gonzalez-Castro A., Llorca J., Ortiz-Melon F., and Minambres E. Early complications of high-dose methylprednisolone in acute spinal cord injury patients. Injury 39 (2008) 748-752
147. Tanga F.Y., Nutile-McMenemy N., and DeLeo J.A. The CNS role of toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proceedings of the National Academy of Sciences of the United States of America 102 (2005) 5856-5861
148. Taoka Y., Okajima K., Uchiba M., Murakami K., Kushimoto S., Johno M., et al. Role of neutrophils in spinal cord injury in the rat. Neuroscience 79 (1997) 1177-1182
149. Temporin K., Tanaka H., Kuroda Y., Okada K., Yachi K., Moritomo H., et al. IL-1beta promotes neurite outgrowth by deactivating RhoA via p38 MAPK pathway. Biochemical and Biophysical Research Communications 365 (2008) 375-380
150. Temporin K., Tanaka H., Kuroda Y., Okada K., Yachi K., Moritomo H., et al. Interleukin-1 beta promotes sensory nerve regeneration after sciatic nerve injury. Neuroscience Letters 440 (2008) 130-133
151. Teng Y.D., Choi H., Onario R.C., Zhu S., Desilets F.C., Lan S., et al. Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury. Proceedings of the National Academy of Sciences of the United States of America 101 (2004) 3071-3076
152. Termeer C., Benedix F., Sleeman J., Fieber C., Voith U., Ahrens T., et al. Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. Journal of Experimental Medicine 195 (2002) 99-111
153. Tikka T.M., and Koistinaho J.E. Minocycline provides neuroprotection against N-methyl-d-aspartate neurotoxicity by inhibiting microglia. Journal of Immunology 166 (2001) 7527-7533
154. Vallieres N., Berard J.L., David S., and Lacroix S. Systemic injections of lipopolysaccharide accelerates myelin phagocytosis during Wallerian degeneration in the injured mouse spinal cord. Glia 53 (2006) 103-113
155. Vargas M.E., and Barres B.A. Why is Wallerian degeneration in the CNS so slow?. Annual Review of Neuroscience 30 (2007) 153-179
156. Vogel C., Stallforth S., and Sommer C. Altered pain behavior and regeneration after nerve injury in TNF receptor deficient mice. Journal of the Peripheral Nervous System 11 (2006) 294-303
157. Wang X.J., Kong K.M., Qi W.L., Ye W.L., and Song P.S. Interleukin-1 beta induction of neuron apoptosis depends on p38 mitogen-activated protein kinase activity after spinal cord injury. Acta Pharmacologica Sinica 26 (2005) 934-942
158. Weber C., Fraemohs L., and Dejana E. The role of junctional adhesion molecules in vascular inflammation. Nature Reviews Immunology 7 (2007) 467-477
159. Wells J.E., Hurlbert R.J., Fehlings M.G., and Yong V.W. Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain 126 (2003) 1628-1637
160. Wieseler-Frank J., Maier S.F., and Watkins L.R. Immune-to-brain communication dynamically modulates pain: physiological and pathological consequences. Brain, Behavior and Immunity 19 (2005) 104-111
161. Wrathall J.R., Teng Y.D., and Marriott R. Delayed antagonism of AMPA/kainate receptors reduces long-term functional deficits resulting from spinal cord trauma. Experimental Neurology 145 (1997) 565-573
162. Xu L., Fagan S.C., Waller J.L., Edwards D., Borlongan C.V., Zheng J., et al. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurology 4 (2004) 7
163. Xu Z., Wang B.-R., Wang X., Kuang F., Duan X.-L., Jiao X.-Y., et al. ERK1/2 and p38 mitogen-activated protein kinase mediate iNOS-induced spinal neuron degeneration after acute traumatic spinal cord injury. Life Sciences 79 (2006) 1895-1905
164. Yang L., Blumbergs P.C., Jones N.R., Manavis J., Sarvestani G.T., and Ghabriel M.N. Early expression and cellular localization of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury. Spine 29 (2004) 966-971
165. Yin Y., Cui Q., Li Y., Irwin N., Fischer D., Harvey A.R., et al. Macrophage-derived factors stimulate optic nerve regeneration. Journal of Neuroscience 23 (2003) 2284-2293
166. Yune T.Y., Lee J.Y., Jung G.Y., Kim S.J., Jiang M.H., Kim Y.C., et al. Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. Journal of Neuroscience 27 (2007) 7751-7761
167. Zang D.W., and Cheema S.S. Leukemia inhibitory factor promotes recovery of locomotor function following spinal cord injury in the mouse. Journal of Neurotrauma 20 (2003) 1215-1222
168. Zhao P., Waxman S.G., and Hains B.C. Modulation of thalamic nociceptive processing after spinal cord injury through remote activation of thalamic microglia by cysteine cysteine chemokine ligand 21. Journal of Neuroscience 27 (2007) 8893-8902