Toll-like receptors in central nervous system injury and disease: A focus on the spinal cord

Brain, Behavior, and Immunity

Volumn 42, Issue , 2014, Pages 232-245

  Heiman, Adee ^a,c   Pallottie, Alexandra ^a,b   Heary, Robert F ^a   Elkabes, Stella ^a  

^a RUTGERS UNIVERSITY   (United States)

^b RUTGERS NEW JERSEY MEDICAL SCHOOL   (United States)

^c University of Louisville School of Medicine   (United States)

Author keywords

Amyotrophic lateral sclerosis; Chemokine; Cytokine; Gliosis; Innate immunity; Motor neuron; Neuropathic pain; Neuroprotection; Regeneration; Spinal cord injury

Indexed keywords

ALPHA CRYSTALLIN; CD14 ANTIGEN; EXCITATORY AMINO ACID TRANSPORTER 1; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 5; TOLL LIKE RECEPTOR 6; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; VESICULAR GLUTAMATE TRANSPORTER 1; ZYMOSAN;

AMYOTROPHIC LATERAL SCLEROSIS; ASTROCYTE; IMMUNOCOMPETENT CELL; MACROPHAGE; MICROGLIA; NEUROPATHIC PAIN; NONHUMAN; OLIGODENDROGLIA; PAIN; PERIPHERAL NERVE INJURY; PROTEIN EXPRESSION; REVIEW; SPINAL CORD INJURY; UPREGULATION; ANIMAL; HUMAN; METABOLISM; PATHOLOGY; SPINAL CORD; SPINAL CORD DISEASE;

ANIMALS; HUMANS; SPINAL CORD; SPINAL CORD DISEASES; SPINAL CORD INJURIES; TOLL-LIKE RECEPTORS;

EID: 84908611891     PISSN: 08891591     EISSN: 10902139     Source Type: Journal    
DOI: 10.1016/j.bbi.2014.06.203     Document Type: Review

References (213)

1. Adhikary S., Li H., Heller J., Skarica M., Zhang M., Ganea D., Tuma R.F. Modulation of inflammatory responses by a cannabinoid-2-selective agonist after spinal cord injury. J. Neurotrauma 2011, 28:2417-2427.
2. Akira S., Takeda K. Toll-like receptor signaling. Nat. Rev. Immunol. 2004, 4:499-511.
3. Alexopoulou L., Holt A.C., Medzhitov R., Flavell R.A. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001, 413:732-738.
4. An H., Xu H., Yu Y., Zhang M., Qi R., Yan X., Liu S., Wang W., Guo Z., Qin Z., Cao X. Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB, ERK and p38 MAPK signal pathways. Immunol. Lett. 2002, 81:165-169.
5. Anderson K.V., Bokla L., Nusslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product. Cell 1985, 42:791-798.
6. Anderson K.V., Jurgens G., Nusslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: genetic studies on the role of the Toll gene product. Cell 1985, 42:779-789.
7. Andrews J.M., Gardner M.B., Wolfgram F.J., Ellison G.W., Porter D.D., Brandkamp W.W. Studies on a murine form of spontaneous lower motor neuron degeneration-the wobbler (wa) mouse. Am. J. Pathol. 1974, 76:63-78.
8. Arruda J.L., Colburn R.W., Rickman A.J., Rutkowski M.D., DeLeo J.A. Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain. Brain Res. Mol. Brain Res. 1998, 62:228-235.
9. Asea A., Rehli M., Kabingu E., Boch J.A., Bare O., Auron P.E., Stevenson M.A., Calderwood S.K. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 2002, 277:15028-15034.
10. Austin P.J., Moalem-Taylor G. The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. J. Neuroimmunol. 2010, 229:26-50.
11. Bandell M., Story G.M., Hwang S.W., Viswanath V., Eid S.R., Petrus M.J., Earley T.J., Patapoutian A. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 2004, 41:849-857.
12. Barnes B.J., Moore P.A., Pitha P.M. Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes. J. Biol. Chem. 2001, 276:23382-23390.
13. Barrot M. Tests and models of nociception and pain in rodents. Neuroscience 2012, 211:39-50.
14. Basbaum A.I., Bautista D.M., Scherrer G., Julius D. Cellular and molecular mechanisms of pain. Cell 2009, 139:267-284.
15. Beers D.R., Henkel J.S., Xiao Q., Zhao W., Wang J., Yen A.A., Siklos L., McKercher S.R., Appel S.H. Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. 2006, 103:16021-16026.
16. Bennett G.J., Xie Y.K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988, 33:87-107.
17. Binns B.C., Huang Y., Goettl V.M., Hackshaw K.V., Stephens R.L. Glutamate uptake is attenuated in spinal deep dorsal and ventral horn in the rat spinal nerve ligation model. Brain Res. 2005, 1041:38-47.
18. Boillee S., Peschanski M., Junier M.P. The wobbler mouse: a neurodegeneration jigsaw puzzle. Mol. Neurobiol. 2003, 28:65-106.
19. Boillee S., Yamanaka K., Lobsiger C.S., Copeland N.G., Jenkins N.A., Kassiotis G., Kollias G., Cleveland D.W. Onset and progression in inherited ALS determined by motor neurons and microglia. Science 2006, 312:1389-1392.
20. Bourke E., Bosisio D., Golay J., Polentarutti N., Mantovani A. The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. Blood 2003, 102:956-963.
21. Bovijn C., Ulrichts P., De Smet A.S., Catteeuw D., Beyaert R., Tavernier J., Peelman F. Identification of interaction sites for dimerization and adapter recruitment in Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 4. J. Biol. Chem. 2012, 287:4088-4098.
22. Bowerman M., Vincent T., Scamps F., Perrin F.E., Camu W., Raoul C. Neuroimmunity dynamics and the development of therapeutic strategies for amyotrophic lateral sclerosis. Front. Cell. Neurosci. 2013, 7:214. 10.3389/fncel.2013.00214.
23. Bowman C.C., Rasley A., Tranguch S.L., Marriott I. Cultured astrocytes express toll-like receptors for bacterial products. Glia 2003, 43:281-291.
24. Brightbill H.D., Libraty D.H., Krutzik S.R., Yang R.B., Belisle J.T., Bleharski J.R., Maitland M., Norgard M.V., Plevy S.E., Smale S.T., Brennan P.J., Bloom B.R., Godowski P.J., Modlin R.L. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 1999, 285:732-736.
25. Bruce J.C., Oatway M.A., Weaver L.C. Chronic pain after clip-compression injury of the rat spinal cord. Exp. Neurol. 2002, 178:33-48.
26. Bruijn L.I., Miller T.M., Cleveland D.W. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu. Rev. Neurosci. 2004, 27:723-749.
27. Bsibsi M., Nomden A., van Noort J.M., Baron W. Toll-like receptors 2 and 3 agonists differentially affect oligodendrocyte survival, differentiation, and myelin membrane formation. J. Neurosci. Res. 2012, 90:388-398.
28. Bsibsi M., Persoon-Deen C., Verwer R.W., Meeuwsen S., Ravid R., Van Noort J.M. Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators. Glia 2006, 53:688-695.
29. Bsibsi M., Ravid R., Gveric D., van Noort J.M. Broad expression of Toll-like receptors in the human central nervous system. J. Neuropathol. Exp. Neurol. 2002, 61:1013-1021.
30. Butchi N.B., Du M., Peterson K.E. Interactions between TLR7 and TLR9 agonists and receptors regulate innate immune responses by astrocytes and microglia. Glia 2010, 58:650-664.
31. Cameron J.S., Alexopoulou L., Sloane J.A., DiBernardo A.B., Ma Y., Kosaras B., Flavell R., Strittmatter S.M., Volpe J., Sidman R., Vartanian T. Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals. J. Neurosci. 2007, 27:13033-13041.
32. Cao L., Tanga F.Y., Deleo J.A. The contributing role of CD14 in toll-like receptor 4 dependent neuropathic pain. Neuroscience 2009, 158:896-903.
33. Casula M., Iyer A.M., Spliet W.G., Anink J.J., Steentjes K., Sta M., Troost D., Aronica E. Toll-like receptor signaling in amyotrophic lateral sclerosis spinal cord tissue. Neuroscience 2011, 179:233-243.
34. Caterina M.J., Schumacher M.A., Tominaga M., Rosen T.A., Levine J.D., Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997, 389:816-824.
35. Chamankhah M., Eftekharpour E., Karimi-Abdolrezaee S., Boutros P.C., San-Marina S., Fehlings M.G. Genome-wide gene expression profiling of stress response in a spinal cord clip compression injury model. BMC Genomics 2013, 14:583. 10.1186/1471-2164-14-583.
36. Chaudhary P.M., Ferguson C., Nguyen V., Nguyen O., Massa H.F., Eby M., Jasmin A., Trask B.J., Hood L., Nelson P.S. Cloning and characterization of two Toll/Interleukin-1 receptor-like genes TIL3 and TIL4: evidence for a multi-gene receptor family in humans. Blood 1998, 91:4020-4027.
37. Chen K.B., Uchida K., Nakajima H., Yayama T., Hirai T., Rodriguez Guerrero A., Kobayashi S., Ma W.Y., Liu S.Y., Zhu P., Baba H. High-mobility group box-1 and its receptors contribute to proinflammatory response in the acute phase of spinal cord injury in rats. Spine 2011, 36:2122-2129.
38. Chiu Y.C., Lin C.Y., Chen C.P., Huang K.C., Tong K.M., Tzeng C.Y., Lee T.S., Hsu H.C., Tang C.H. Peptidoglycan enhances IL-6 production in human synovial fibroblasts via TLR2 receptor, focal adhesion kinase, Akt, and AP-1-dependent pathway. J. Immunol. 2009, 183:2785-2792.
39. Chuang T., Ulevitch R.J. Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells. Biochim. Biophys. Acta 2001, 1518:157-161.
40. Chuang T.H., Ulevitch R.J. Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9. Eur. Cytokine Netw. 2000, 11:372-378.
41. Clark A.K., D'Aquisto F., Gentry C., Marchand F., McMahon S.B., Malcangio M. Rapid co-release of interleukin 1beta and caspase 1 in spinal cord inflammation. J. Neurochem. 2006, 99:868-880.
42. Clark A.K., Staniland A.A., Marchand F., Kaan T.K., McMahon S.B., Malcangio M. P2X7-dependent release of interleukin-1beta and nociception in the spinal cord following lipopolysaccharide. J. Neurosci. 2010, 30:573-582.
43. Clement A.M., Nguyen M.D., Roberts E.A., Garcia M.L., Boillee S., Rule M., McMahon A.P., Doucette W., Siwek D., Ferrante R.J., Brown R.H., Julien J.P., Goldstein L.S., Cleveland D.W. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 2003, 302:113-117.
44. Coull J.A., Beggs S., Boudreau D., Boivin D., Tsuda M., Inoue K., Gravel C., Salter M.W., De Koninck Y. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005, 438:1017-1021.
45. Coyle D.E. Partial peripheral nerve injury leads to activation of astroglia and microglia which parallels the development of allodynic behavior. Glia 1998, 23:75-83.
46. Cunha F.Q., Poole S., Lorenzetti B.B., Ferreira S.H. The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br. J. Pharmacol. 1992, 107:660-664.
47. Daemen M.A., Hoogland G., Cijntje J.M., Spincemaille G.H. Upregulation of the GABA-transporter GAT-1 in the spinal cord contributes to pain behaviour in experimental neuropathy. Neurosci. Lett. 2008, 444:112-115.
48. David B.T., Ratnayake A., Amarante M.A., Reddy N.P., Dong W., Sampath S., Heary R.F., Elkabes S. A toll-like receptor 9 antagonist reduces pain hypersensitivity and the inflammatory response in spinal cord injury. Neurobiol. Dis. 2013, 54:194-205.
49. David B.T., Sampath S., Dong W., Heiman A., Rella C.E., Elkabes S., Heary R.F. A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury. J. Neurotrauma 2014, in press.
50. De Paola M., Mariani P., Bigini P., Peviani M., Ferrara G., Molteni M., Gemma S., Veglianese P., Castellaneta V., Boldrin V., Rossetti C., Chiabrando C., Forloni G., Mennini T., Fanelli R. Neuroprotective effects of toll-like receptor antagonism in spinal cord cultures and in a mouse model of motor neuron degeneration. Mol. Med. 2012, 18:971-981.
51. Desnues B., Macedo A.B., Roussel-Queval A., Bonnardel J., Henri S., Demaria O., Alexopoulou L. TLR8 on dendritic cells and TLR9 on B cells restrain TLR7-mediated spontaneous autoimmunity in C57BL/6 mice. Proc. Natl. Acad. Sci. 2014, 111:1497-1502.
52. Detloff M.R., Fisher L.C., McGaughy V., Longbrake E.E., Popovich P.G., 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. Exp. Neurol. 2008, 212:337-347.
53. Diebold S.S., Kaisho T., Hemmi H., Akira S., Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004, 303:1529-1531.
54. Drew G.M., Siddall P.J., Duggan A.W. Mechanical allodynia following contusion injury of the rat spinal cord is associated with loss of GABAergic inhibition in the dorsal horn. Pain 2004, 109:379-388.
55. Du X., Poltorak A., Wei Y., Beutler B. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur. Cytokine Netw. 2000, 11:362-371.
56. Dworkin R.H., Backonja M., Rowbotham M.C., Allen R.R., Argoff C.R., Bennett G.J., Bushnell M.C., Farrar J.T., Galer B.S., Haythornthwaite J.A., Hewitt D.J., Loeser J.D., Max M.B., Saltarelli M., Schmader K.E., Stein C., Thompson D., Turk D.C., Wallace M.S., Watkins L.R., Weinstein S.M. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch. Neurol. 2003, 60:1524-1534.
57. Dworkin R.H., Corbin A.E., Young J.P., Sharma U., LaMoreaux L., Bockbrader H., Garofalo E.A., Poole R.M. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2003, 60:1274-1283.
58. Felts P.A., Woolston A.M., Fernando H.B., Asquith S., Gregson N.A., Mizzi O.J., Smith K.J. Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide. Brain 2005, 128:1649-1666.
59. Ferreira S.H., Lorenzetti B.B., Bristow A.F., Poole S. Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue. Nature 1988, 334:698-700.
60. Fitzgerald K.A., Rowe D.C., Barnes B.J., Caffrey D.R., Visintin A., Latz E., Monks B., Pitha P.M., Golenbock D.T. LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J. Exp. Med. 2003, 198:1043-1055.
61. Freria C.M., Velloso L.A., Oliveira A.L. Opposing effects of Toll-like receptors 2 and 4 on synaptic stability in the spinal cord after peripheral nerve injury. J. Neuroinflammation 2012, 9:240. 10.1186/1742-2094-9-240.
62. Freynhagen R., Strojek K., Griesing T., Whalen E., Balkenohl M. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pain 2005, 115:254-263. Epub 2005 Apr 18.
63. Garrison C.J., Dougherty P.M., Kajander K.C., Carlton S.M. Staining of glial fibrillary acidic protein (GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury. Brain Res. 1991, 565:1-7.
64. Gensel J.C., Nakamura S., Guan Z., van Rooijen N., Ankeny D.P., Popovich P.G. Macrophages promote axon regeneration with concurrent neurotoxicity. J. Neurosci. 2009, 29:3956-3968.
65. Gondokaryono S.P., Ushio H., Niyonsaba F., Hara M., Takenaka H., Jayawardana S.T., Ikeda S., Okumura K., Ogawa H. The extra domain A of fibronectin stimulates murine mast cells via toll-like receptor 4. J. Leukoc. Biol. 2007, 82:657-665.
66. Gregory N.S., Harris A.L., Robinson C.R., Dougherty P.M., Fuchs P.N., Sluka K.A. An overview of animal models of pain: disease models and outcome measures. J. Pain 2013, 14:1255-1269.
67. Guth L., Zhang Z., DiProspero N.A., Joubin K., Fitch M.T. Spinal cord injury in the rat: treatment with bacterial lipopolysaccharide and indomethacin enhances cellular repair and locomotor function. Exp. Neurol. 1994, 126:76-87.
68. Gwak Y.S., Hulsebosch C.E. Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat. Neuroscience 2009, 161:895-903.
69. Hains B.C., Waxman S.G. Activated microglia contribute to the maintenance of chronic pain after spinal cord injury. J. Neurosci. 2006, 26:4308-4317.
70. Hajjar A.M., O'Mahony D.S., Ozinsky A., Underhill D.M., Aderem A., Klebanoff S.J., Wilson C.B. Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin. J. Immunol. 2001, 166:15-19.
71. Halfon M.S., Hashimoto C., Keshishian H. The Drosophila toll gene functions zygotically and is necessary for proper motoneuron and muscle development. Dev. Biol. 1995, 169:151-167.
72. Hall E.D., Oostveen J.A., Gurney M.E. Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS. Glia 1998, 23:249-256.
73. Han K.J., Su X., Xu L.G., Bin L.H., Zhang J., Shu H.B. Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways. J. Biol. Chem. 2004, 279:15652-15661.
74. Hasan U., Chaffois C., Gaillard C., Saulnier V., Merck E., Tancredi S., Guiet C., Briere F., Vlach J., Lebecque S., Trinchieri G., Bates E.E. Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J. Immunol. 2005, 174:2942-2950.
75. Hashimoto C., Hudson K.L., Anderson K.V. The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein. Cell 1988, 52:269-279.
76. Hausmann O.N. Post-traumatic inflammation following spinal cord injury. Spinal cord 2003, 41:369-378.
77. Hayashi F., Smith K.D., Ozinsky A., Hawn T.R., Yi E.C., Goodlett D.R., Eng J.K., Akira S., Underhill D.M., Aderem A. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 2001, 410:1099-1103.
78. Heil F., Hemmi H., Hochrein H., Ampenberger F., Kirschning C., Akira S., Lipford G., Wagner H., Bauer S. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004, 303:1526-1529.
79. Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., Matsumoto M., Hoshino K., Wagner H., Takeda K., Akira S. A Toll-like receptor recognizes bacterial DNA. Nature 2000, 408:740-745.
80. Hirschfeld M., Kirschning C.J., Schwandner R., Wesche H., Weis J.H., Wooten R.M., Weis J.J. Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2. J. Immunol. 1999, 163:2382-2386.
81. Hornung V., Rothenfusser S., Britsch S., Krug A., Jahrsdorfer B., Giese T., Endres S., Hartmann G. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 2002, 168:4531-4537.
82. Huang H., Evankovich J., Yan W., Nace G., Zhang L., Ross M., Liao X., Billiar T., Xu J., Esmon C.T., Tsung A. Endogenous histones function as alarmins in sterile inflammatory liver injury through Toll-like receptor 9 in mice. Hepatology 2011, 54:999-1008.
83. Hutchinson M.R., Zhang Y., Brown K., Coats B.D., Shridhar M., Sholar P.W., Patel S.J., Crysdale N.Y., Harrison J.A., Maier S.F., Rice K.C., Watkins L.R. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur. J. Neurosci. 2008, 28:20-29.
84. Hutchinson M.R., Ramos K.M., Loram L.C., Wieseler J., Sholar P.W., Kearney J.J., Lewis M.T., Crysdale N.Y., Zhang Y., Harrison J.A., Maier S.F., Rice K.C., Watkins L.R. Evidence for a role of heat shock protein-90 in toll like receptor 4 mediated pain enhancement in rats. Neuroscience 2009, 164:1821-1832.
85. Johnston J.A., Dalton M.J., Gurney M.E., Kopito R.R. Formation of high molecular weight complexes of mutant Cu, Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. 2000, 97:12571-12576.
86. Kadowaki N., Ho S., Antonenko S., Malefyt R.W., Kastelein R.A., Bazan F., Liu Y.J. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J. Exp. Med. 2001, 194:863-869.
87. Kaisho T., Akira S. Toll-like receptor function and signaling. J. Allergy Clin. Immunol. 2006, 117:979-987.
88. Kariko K., Buckstein M., Ni H., Weissman D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 2005, 23:165-175.
89. Kawai T., Adachi O., Ogawa T., Takeda K., Akira S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 1999, 11:115-122.
90. 2+ concentration in the spinal dorsal horn in an animal model of neuropathic pain. Pain 1996, 68:85-96.
91. Kigerl K.A., Lai W., Rivest S., Hart R.P., Satoskar A.R., Popovich P.G. Toll-like receptor (TLR)-2 and TLR-4 regulate inflammation, gliosis, and myelin sparing after spinal cord injury. J. Neurochem. 2007, 102:37-50.
92. Kim D., Kim M.A., Cho I.H., Kim M.S., Lee S., Jo E.K., Choi S.Y., Park K., Kim J.S., Akira S., Na H.S., Oh S.B., Lee S.J. A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. J. Biol. Chem. 2007, 282:14975-14983.
93. Klopstein A., Santos-Nogueira E., Francos-Quijorna I., Redensek A., David S., Navarro X., Lopez-Vales R. Beneficial effects of alphaB-crystallin in spinal cord contusion injury. J. Neurosci. 2012, 32:14478-14488.
94. Kohno T., Ji R.R., Ito N., Allchorne A.J., Befort K., Karchewski L.A., Woolf C.J. Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord. Pain 2005, 117:77-87.
95. Koltzenburg M., Scadding J. Neuropathic pain. Curr. Opin. Neurol. 2001, 14:641-647.
96. Kuang X., Huang Y., Gu H.F., Zu X.Y., Zou W.Y., Song Z.B., Guo Q.L. Effects of intrathecal epigallocatechin gallate, an inhibitor of Toll-like receptor 4, on chronic neuropathic pain in rats. Eur. J. Pharmacol. 2012, 676:51-56.
97. Kwiatkowski T.J., Bosco D.A., Leclerc A.L., Tamrazian E., Vanderburg C.R., Russ C., Davis A., Gilchrist J., Kasarskis E.J., Munsat T., Valdmanis P., Rouleau G.A., Hosler B.A., Cortelli P., de Jong P.J., Yoshinaga Y., Haines J.L., Pericak-Vance M.A., Yan J., Ticozzi N., Siddique T., McKenna-Yasek D., Sapp P.C., Horvitz H.R., Landers J.E., Brown R.H. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009, 323:1205-1208.
98. Laflamme N., Soucy G., Rivest S. Circulating cell wall components derived from gram-negative, not gram-positive, bacteria cause a profound induction of the gene-encoding Toll-like receptor 2 in the CNS. J. Neurochem. 2001, 79:648-657.
99. Lafon M., Megret F., Lafage M., Prehaud C. The innate immune facet of brain: human neurons express TLR-3 and sense viral dsRNA. J. Mol. Neurosci. 2006, 29:185-194.
100. Latz E., Verma A., Visintin A., Gong M., Sirois C.M., Klein D.C., Monks B.G., McKnight C.J., Lamphier M.S., Duprex W.P., Espevik T., Golenbock D.T. Ligand-induced conformational changes allosterically activate Toll-like receptor 9. Nat. Immunol. 2007, 8:772-779.
101. Lehmann S.M., Kruger C., Park B., Derkow K., Rosenberger K., Baumgart J., Trimbuch T., Eom G., Hinz M., Kaul D., Habbel P., Kalin R., Franzoni E., Rybak A., Nguyen D., Veh R., Ninnemann O., Peters O., Nitsch R., Heppner F.L., Golenbock D., Schott E., Ploegh H.L., Wulczyn F.G., Lehnardt S. An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration. Nat. Neurosci. 2012, 15:827-835.
102. Lehnardt S., Schott E., Trimbuch T., Laubisch D., Krueger C., Wulczyn G., Nitsch R., Weber J.R. 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. J. Neurosci. 2008, 28:2320-2331.
103. Lemaitre B., Nicolas E., Michaut L., Reichhart J.M., Hoffmann J.A. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996, 86:973-983.
104. Lepore A.C., O'Donnell J., Bonner J.F., Paul C., Miller M.E., Rauck B., Kushner R.A., Rothstein J.D., Fischer I., Maragakis N.J. Spatial and temporal changes in promoter activity of the astrocyte glutamate transporter GLT1 following traumatic spinal cord injury. J. Neurosci. Res. 2011, 89:1001-1017.
105. Lepore A.C., O'Donnell J., Kim A.S., Yang E.J., Tuteja A., Haidet-Phillips A., O'Banion C.P., Maragakis N.J. Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury. Glia 2011, 59:1996-2005.
106. Letiembre M., Liu Y., Walter S., Hao W., Pfander T., Wrede A., Schulz-Schaeffer W., Fassbender K. Screening of innate immune receptors in neurodegenerative diseases: a similar pattern. Neurobiol. Aging 2009, 30:759-768.
107. Lewin G.R., Rueff A., Mendell L.M. Peripheral and central mechanisms of NGF-induced hyperalgesia. Eur. J. Neurosci. 1994, 6:1903-1912.
108. Lewis S.S., Loram L.C., Hutchinson M.R., Li C.M., Zhang Y., Maier S.F., Huang Y., Rice K.C., Watkins L.R. (+)-Naloxone, an opioid-inactive toll-like receptor 4 signaling inhibitor, reverses multiple models of chronic neuropathic pain in rats. J. Pain 2012, 13:498-506.
109. Lim H., Kim D., Lee S.J. Toll-like receptor 2 mediates peripheral nerve injury-induced NADPH oxidase 2 expression in spinal cord microglia. J. Biol. Chem. 2013, 288:7572-7579.
110. Liu L., Botos I., Wang Y., Leonard J.N., Shiloach J., Segal D.M., Davies D.R. Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 2008, 320:379-381.
111. Liu W., Ouyang X., Yang J., Liu J., Li Q., Gu Y., Fukata M., Lin T., He J.C., Abreu M., Unkeless J.C., Mayer L., Xiong H. AP-1 activated by toll-like receptors regulates expression of IL-23 p19. J. Biol. Chem. 2009, 284:24006-24016.
112. Liu Y., Hao W., Dawson A., Liu S., Fassbender K. Expression of amyotrophic lateral sclerosis-linked SOD1 mutant increases the neurotoxic potential of microglia via TLR2. J. Biol. Chem. 2009, 284:3691-3699.
113. Liu T., Berta T., Xu Z.Z., Park C.K., Zhang L., Lu N., Liu Q., Liu Y., Gao Y.J., Liu Y.C., Ma Q., Dong X., Ji R.R. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J. Clin. Invest. 2012, 122:2195-2207.
114. Louis J.C., Magal E., Takayama S., Varon S. CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science 1993, 259:689-692.
115. Ma Y., Li J., Chiu I., Wang Y., Sloane J.A., Lu J., Kosaras B., Sidman R.L., Volpe J.J., Vartanian T. Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. J. Cell Biol. 2006, 175:209-215.
116. Malmberg A.B., Basbaum A.I. Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates. Pain 1998, 76:215-222.
117. Mautes A.E., Noble L.J. Co-induction of HSP70 and heme oxygenase-1 in macrophages and glia after spinal cord contusion in the rat. Brain Res. 2000, 883:233-237.
118. Mayer M., Bhakoo K., Noble M. Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro. Development 1994, 120:143-153.
119. McKemy D.D., Neuhausser W.M., Julius D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 2002, 416:52-58.
120. Medzhitov R., Preston-Hurlburt P., Janeway C.A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997, 388:394-397.
121. Medzhitov R., Preston-Hurlburt P., Kopp E., Stadlen A., Chen C., Ghosh S., Janeway C.A. MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol. Cell 1998, 2:253-258.
122. Medzhitov R., Janeway C. Innate immune recognition: mechanisms and pathways. Immunol. Rev. 2000, 173:89-97.
123. Mei X.P., Zhou Y., Wang W., Tang J., Wang W., Zhang H., Xu L.X., Li Y.Q. Ketamine depresses toll-like receptor 3 signaling in spinal microglia in a rat model of neuropathic pain. Neurosignals 2011, 19:44-53.
124. Meisner J.G., Marsh A.D., Marsh D.R. Loss of GABAergic interneurons in laminae I-III of the spinal cord dorsal horn contributes to reduced GABAergic tone and neuropathic pain after spinal cord injury. J. Neurotrauma 2010, 27:729-737.
125. Meller S.T., Dykstra C., Grzybycki D., Murphy S., Gebhart G.F. The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat. Neuropharmacology 1994, 33:1471-1478.
126. Moody M.A., Santra S., Vandergrift N.A., Sutherland L.L., Gurley T.C., Drinker M.S., Allen A.A., Xia S.M., Meyerhoff R.R., Parks R., Lloyd K.E., Easterhoff D., Alam S.M., Liao H.X., Ward B.M., Ferrari G., Montefiori D.C., Tomaras G.D., Seder R.A., Letvin N.L., Haynes B.F. TLR-7/8 and 9 agonists cooperate to enhance HIV-1 envelope antibody responses in rhesus macaques. J. Virol. 2014, 88:3329-3339.
127. Moore K.A., Kohno T., Karchewski L.A., Scholz J., Baba H., Woolf C.J. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J. Neurosci. 2002, 22:6724-6731.
128. Moore R.A., Wiffen P.J., Derry S., McQuay H.J. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst. Rev. 2011, CD007938. 10.1002/14651858.CD007938.pub3.
129. Mukundan L., Bishop G.A., Head K.Z., Zhang L., Wahl L.M., Suttles J. TNF receptor-associated factor 6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages. J. Immunol. 2005, 174:1081-1109.
130. Muzio M., Natoli G., Saccani S., Levrero M., Mantovani A. The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J. Exp. Med. 1998, 187:2097-2101.
131. Muzio M., Bosisio D., Polentarutti N., D'Amico G., Stoppacciaro A., Mancinelli R., van't Veer C., Penton-Rol G., Ruco L.P., Allavena P., Mantovani A. Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J. Immunol. 2000, 164:5998-6004.
132. Nagai M., Re D.B., Nagata T., Chalazonitis A., Jessell T.M., Wichterle H., Przedborski S. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat. Neurosci. 2007, 10:615-622.
133. Neumann M., Sampathu D.M., Kwong L.K., Truax A.C., Micsenyi M.C., Chou T.T., Bruce J., Schuck T., Grossman M., Clark C.M., McCluskey L.F., Miller B.L., Masliah E., Mackenzie I.R., Feldman H., Feiden W., Kretzschmar H.A., Trojanowski J.Q., Lee V.M. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006, 314:130-133.
134. Newcomb R., Sun X., Taylor L., Curthoys N., Giffard R.G. Increased production of extracellular glutamate by the mitochondrial glutaminase following neuronal death. J. Biol. Chem. 1997, 272:11276-11282.
135. Nguyen M.D., D'Aigle T., Gowing G., Julien J.P., Rivest S. Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis. J. Neurosci. 2004, 24:1340-1349.
136. Nicotra L., Loram L.C., Watkins L.R., Hutchinson M.R. Toll-like receptors in chronic pain. Exp. Neurol. 2012, 234:316-329.
137. Nishimura M., Naito S. Tissue-specific mRNA expression profiles of human toll-like receptors and related genes. Biol. Pharm. Bull. 2005, 28:886-892.
138. Oatway M.A., Chen Y., Weaver L.C. The 5-HT3 receptor facilitates at-level mechanical allodynia following spinal cord injury. Pain 2004, 110:259-268.
139. Ohashi K., Burkart V., Flohe S., Kolb H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J. Immunol. 2000, 164:558-561.
140. Okun E., Barak B., Saada-Madar R., Rothman S.M., Griffioen K.J., Roberts N., Castro K., Mughal M.R., Pita M.A., Stranahan A.M., Arumugam T.V., Mattson M.P. Evidence for a developmental role for TLR4 in learning and memory. PLoS ONE 2012, 7:e47522. doi: 0.1371/journal.pone.0047522.
141. Olsen M.L., Campbell S.C., McFerrin M.B., Floyd C.L., Sontheimer H. Spinal cord injury causes a wide-spread, persistent loss of Kir4.1 and glutamate transporter 1: benefit of 17 beta-oestradiol treatment. Brain 2010, 133:1013-1025.
142. Ousman S.S., Tomooka B.H., van Noort J.M., Wawrousek E.F., O'Connor K.C., Hafler D.A., Sobel R.A., Robinson W.H., Steinman L. Protective and therapeutic role for alphaB-crystallin in autoimmune demyelination. Nature 2007, 448:474-479.
143. Ozinsky A., Smith K.D., Hume D., Underhill D.M. Co-operative induction of pro-inflammatory signaling by Toll-like receptors. J. Endotoxin Res. 2000, 6:393-396.
144. Ozinsky A., Underhill D.M., Fontenot J.D., Hajjar A.M., Smith K.D., Wilson C.B., Schroeder L., Aderem A. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Natl. Acad. Sci. 2000, 97:13766-13771.
145. Park J.S., Svetkauskaite D., He Q., Kim J.Y., Strassheim D., Ishizaka A., Abraham E. Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J. Biol. Chem. 2004, 279:7370-7377.
146. Peier A.M., Moqrich A., Hergarden A.C., Reeve A.J., Andersson D.A., Story G.M., Earley T.J., Dragoni I., McIntyre P., Bevan S., Patapoutian A. A TRP channel that senses cold stimuli and menthol. Cell 2002, 108:705-715.
147. Poltorak A., He X., Smirnova I., Liu M.Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M., Galanos C., Freudenberg M., Ricciardi-Castagnoli P., Layton B., Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998, 282:2085-2088.
148. Poltorak A., Smirnova I., He X., Liu M.Y., Van Huffel C., McNally O., Birdwell D., Alejos E., Silva M., Du X., Thompson P., Chan E.K., Ledesma J., Roe B., Clifton S., Vogel S.N., Beutler B. Genetic and physical mapping of the Lps locus: identification of the toll-4 receptor as a candidate gene in the critical region. Blood Cells Mol. Dis. 1998, 24:340-355.
149. Popovich P.G., Wei P., Stokes B.T. The cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J. Comp. Neurol. 1997, 377:443-464.
150. Popovich P.G., Guan Z., McGaughy V., Fisher L., Hickey W.F., Basso D.M. The neuropathological and behavioral consequences of intraspinal microglial/macrophage activation. J. Neuropathol. Exp. Neurol. 2002, 61:623-633.
151. Qiu P., Pan P.C., Govind S. A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. Development 1998, 125:1909-1920.
152. Rainero I., Pinessi L., Tsuda T., Vignocchi M.G., Vaula G., Calvi L., Cerrato P., Rossi B., Bergamini L., McLachlan D.R., et al. SOD1 missense mutation in an Italian family with ALS. Neurology 1994, 44:347-349.
153. Rahman W., D'Mello R., Dickenson A.H. Peripheral nerve injury-induced changes in spinal alpha(2)-adrenoceptor-mediated modulation of mechanically evoked dorsal horn neuronal responses. J. Pain 2008, 9:350-359.
154. Reeve A.J., Patel S., Fox A., Walker K., Urban L. Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat. Eur. J. Pain 2000, 4:247-257.
155. Renton A.E., Chio A., Traynor B.J. State of play in amyotrophic lateral sclerosis genetics. Nat. Neurosci. 2014, 17:17-23.
156. Rock F.L., Hardiman G., Timans J.C., Kastelein R.A., Bazan J.F. A family of human receptors structurally related to Drosophila Toll. Proc. Natl. Acad. Sci. 1998, 95:588-593.
157. Rosen D.R. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993, 364:59-62.
158. Rowbotham M.C., Twilling L., Davies P.S., Reisner L., Taylor K., Mohr D. Oral opioid therapy for chronic peripheral and central neuropathic pain. N. Engl. J. Med. 2003, 348:1223-1232.
159. Sabroe I., Jones E.C., Usher L.R., Whyte M.K., Dower S.K. Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a critical role for monocytes in leukocyte lipopolysaccharide responses. J. Immunol. 2002, 168:4701-4710.
160. Saito O., Svensson C.I., Buczynski M.W., Wegner K., Hua X.Y., Codeluppi S., Schaloske R.H., Deems R.A., Dennis E.A., Yaksh T.L. Spinal glial TLR4-mediated nociception and production of prostaglandin E(2) and TNF. Br. J. Pharmacol. 2010, 160:1754-1764.
161. Sasai M., Yamamoto M. Pathogen recognition receptors: ligands and signaling pathways by Toll-like receptors. Int. Rev. Immunol. 2013, 32:116-133.
162. Sato M., Tanaka N., Hata N., Oda E., Taniguchi T. Involvement of the IRF family transcription factor IRF-3 in virus-induced activation of the IFN-beta gene. FEBS Lett. 1998, 425:112-116.
163. Sato M., Hata N., Asagiri M., Nakaya T., Taniguchi T., Tanaka N. Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7. FEBS Lett. 1998, 441:106-110.
164. Sato S., Sugiyama M., Yamamoto M., Watanabe Y., Kawai T., Takeda K., Akira S. Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. J. Immunol. 2003, 171:4304-4310.
165. Saval A., Chiodo A.E. Intrathecal baclofen for spasticity management: a comparative analysis of spasticity of spinal vs cortical origin. J. Spinal Cord Med. 2010, 33:16-21.
166. Scaffidi P., Misteli T., Bianchi M.E. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002, 418:191-195.
167. Schaefer L., Babelova A., Kiss E., Hausser H.J., Baliova M., Krzyzankova M., Marsche G., Young M.F., Mihalik D., Gotte M., Malle E., Schaefer R.M., Grone H.J. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J. Clin. Invest. 2005, 115:2223-2233.
168. Schmitt-John T., Drepper C., Mussmann A., Hahn P., Kuhlmann M., Thiel C., Hafner M., Lengeling A., Heimann P., Jones J.M., Meisler M.H., Jockusch H. Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse. Nat. Genet. 2005, 37:1213-1215.
169. Schonberg D.L., Popovich P.G., McTigue D.M. Oligodendrocyte generation is differentially influenced by toll-like receptor (TLR) 2 and TLR4-mediated intraspinal macrophage activation. J. Neuropathol. Exp. Neurol. 2007, 66:1124-1135.
170. Schwei M.J., Honore P., Rogers S.D., Salak-Johnson J.L., Finke M.P., Ramnaraine M.L., Clohisy D.R., Mantyh P.W. Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. J. Neurosci. 1999, 19:10886-10897.
171. Sebastiani G., Leveque G., Lariviere L., Laroche L., Skamene E., Gros P., Malo D. Cloning and characterization of the murine toll-like receptor 5 (Tlr5) gene: sequence and mRNA expression studies in Salmonella-susceptible MOLF/Ei mice. Genomics 2000, 64:230-240.
172. Seltzer Z., Dubner R., Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990, 43:205-218.
173. Seltzer Z., Cohn S., Ginzburg R., Beilin B. Modulation of neuropathic pain behavior in rats by spinal disinhibition and NMDA receptor blockade of injury discharge. Pain 1991, 45:69-75.
174. Shi Z., Cai Z., Sanchez A., Zhang T., Wen S., Wang J., Yang J., Fu S., Zhang D. A novel Toll-like receptor that recognizes vesicular stomatitis virus. J. Biol. Chem. 2011, 286:4517-4524.
175. Shi X.Q., Zekki H., Zhang J. The role of TLR2 in nerve injury-induced neuropathic pain is essentially mediated through macrophages in peripheral inflammatory response. Glia 2011, 59:231-241.
176. Sloane J.A., Batt C., Ma Y., Harris Z.M., Trapp B., Vartanian T. Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2. Proc. Natl. Acad. Sci. 2010, 107:11555-11560.
177. Smiley S.T., King J.A., Hancock W.W. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J. Immunol. 2001, 167:2887-2894.
178. Sorge R.E., LaCroix-Fralish M.L., Tuttle A.H., Sotocinal S.G., Austin J.S., Ritchie J., Chanda M.L., Graham A.C., Topham L., Beggs S., Salter M.W., Mogil J.S. Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice. J. Neurosci. 2011, 31:15450-15454.
179. Sroga J.M., Jones T.B., Kigerl K.A., McGaughty V.M., Popovich P.G. Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J. Comp. Neurol. 2003, 462:223-240.
180. Stirling D.P., Cummins K., Mishra M., Teo W., Yong V.W., Stys P. Toll-like receptor 2-mediated alternative activation of microglia is protective after spinal cord injury. Brain 2014, 137:707-723. Epub 2013 Dec 4.
181. Stokes J.A., Cheung J., Eddinger K., Corr M., Yaksh T.L. Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice. J. Neuroinflammation 2013, 10:148.
182. Stokes J.A., Corr M., Yaksh T.L. Spinal toll-like receptor signaling and nociceptive processing: regulatory balance between TIRAP and TRIF cascades mediated by TNF and IFNbeta. Pain 2013, 154:733-742.
183. Struve J., Maher P.C., Li Y.Q., Kinney S., Fehlings M.G., Kuntz C.T., Sherman L.S. Disruption of the hyaluronan-based extracellular matrix in spinal cord promotes astrocyte proliferation. Glia 2005, 52:16-24.
184. Sugimoto T., Bennett G.J., Kajander K.C. Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine. Pain 1990, 42:205-213.
185. Sung B., Lim G., Mao J. Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. J. Neurosci. 2003, 23:2899-2910.
186. Takaoka A., Yanai H., Kondo S., Duncan G., Negishi H., Mizutani T., Kano S., Honda K., Ohba Y., Mak T.W., Taniguchi T. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 2005, 434:243-249.
187. Takasaki I., Andoh T., Shiraki K., Kuraishi Y. Allodynia and hyperalgesia induced by herpes simplex virus type-1 infection in mice. Pain 2000, 86:95-101.
188. Takeuchi O., Hoshino K., Kawai T., Sanjo H., Takada H., Ogawa T., Takeda K., Akira S. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 1999, 11:443-451.
189. Takeuchi O., Kawai T., Sanjo H., Copeland N.G., Gilbert D.J., Jenkins N.A., Takeda K., Akira S. TLR6: A novel member of an expanding toll-like receptor family. Gene 1999, 231:59-65.
190. Takeuchi O., Takeda K., Hoshino K., Adachi O., Ogawa T., Akira S. Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int. Immunol. 2000, 12:113-117.
191. Tanga F.Y., Nutile-McMenemy N., DeLeo J.A. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc. Natl. Acad. Sci. 2005, 102:5856-5861.
192. Termeer C., Benedix F., Sleeman J., Fieber C., Voith U., Ahrens T., Miyake K., Freudenberg M., Galanos C., Simon J.C. Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. J. Exp. Med. 2002, 195:99-111.
193. Triantafilou M., Triantafilou K. Heat-shock protein 70 and heat-shock protein 90 associate with Toll-like receptor 4 in response to bacterial lipopolysaccharide. Biochem. Soc. Trans. 2004, 32:636-639.
194. Tsuda T., Munthasser S., Fraser P.E., Percy M.E., Rainero I., Vaula G., Pinessi L., Bergamini L., Vignocchi G., McLachlan D.R., et al. Analysis of the functional effects of a mutation in SOD1 associated with familial amyotrophic lateral sclerosis. Neuron 1994, 13:727-736.
195. Turner M.R., Osei-Lah A.D., Hammers A., Al-Chalabi A., Shaw C.E., Andersen P.M., Brooks D.J., Leigh P.N., Mills K.R. Abnormal cortical excitability in sporadic but not homozygous D90A SOD1 ALS. J. Neurol. Neurosurg. Psychiatry 2005, 76:1279-1285.
196. Turner M.R., Hardiman O., Benatar M., Brooks B.R., Chio A., de Carvalho M., Ince P.G., Lin C., Miller R.G., Mitsumoto H., Nicholson G., Ravits J., Shaw P.J., Swash M., Talbot K., Traynor B.J., Van den Berg L.H., Veldink J.H., Vucic S., Kiernan M.C. Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurol. 2013, 12:310-322.
197. Urushitani M., Sik A., Sakurai T., Nukina N., Takahashi R., Julien J.P. Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis. Nat. Neurosci. 2006, 9:108-118.
198. Vallieres N., Berard J.L., David S., Lacroix S. Systemic injections of lipopolysaccharide accelerates myelin phagocytosis during Wallerian degeneration in the injured mouse spinal cord. Glia 2006, 53:103-113.
199. Valori C.F., Brambilla L., Martorana F., Rossi D. The multifaceted role of glial cells in amyotrophic lateral sclerosis. Cell. Mol. Life Sci. 2014, 71:287-297.
200. Van Den Bosch L. Genetic rodent models of amyotrophic lateral sclerosis. J. Biomed. Biotechnol. 2011, 2011:1-11.
201. van Noort J.M., Bsibsi M., Nacken P.J., Gerritsen W.H., Amor S., Holtman I.R., Boddeke E., van Ark I., Leusink-Muis T., Folkerts G., Hennink W.E., Amidi M. Activation of an immune-regulatory macrophage response and inhibition of lung inflammation in a mouse model of COPD using heat-shock protein alpha B-crystallin-loaded PLGA microparticles. Biomaterials 2013, 34:831-840.
202. Vance C., Rogelj B., Hortobagyi T., De Vos K.J., Nishimura A.L., Sreedharan J., Hu X., Smith B., Ruddy D., Wright P., Ganesalingam J., Williams K.L., Tripathi V., Al-Saraj S., Al-Chalabi A., Leigh P.N., Blair I.P., Nicholson G., de Belleroche J., Gallo J.M., Miller C.C., Shaw C.E. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009, 323:1208-1211.
203. Woolf C.J. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983, 306:686-688.
204. Woolf C.J., Safieh-Garabedian B., Ma Q.P., Crilly P., Winter J. Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. Neuroscience 1994, 62:327-331.
205. Wu F.X., Bian J.J., Miao X.R., Huang S.D., Xu X.W., Gong D.J., Sun Y.M., Lu Z.J., Yu W.F. Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain. Int. J. Med. Sci. 2010, 7:251-259.
206. Yamamoto M., Sato S., Hemmi H., Hoshino K., Kaisho T., Sanjo H., Takeuchi O., Sugiyama M., Okabe M., Takeda K., Akira S. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 2003, 301:640-643.
207. Yamamoto M., Sato S., Hemmi H., Sanjo H., Uematsu S., Kaisho T., Hoshino K., Takeuchi O., Kobayashi M., Fujita T., Takeda K., Akira S. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 2002, 420:324-329.
208. Yu M., Wang H., Ding A., Golenbock D.T., Latz E., Czura C.J., Fenton M.J., Tracey K.J., Yang H. HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock 2006, 26:174-179.
209. Zhang F.X., Kirschning C.J., Mancinelli R., Xu X.P., Jin Y., Faure E., Mantovani A., Rothe M., Muzio M., Arditi M. Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J. Biol. Chem. 1999, 274:7611-7614.
210. Zhang D., Zhang G., Hayden M.S., Greenblatt M.B., Bussey C., Flavell R.A., Ghosh S. A toll-like receptor that prevents infection by uropathogenic bacteria. Science 2004, 303:1522-1526.
211. Zhang Q., Raoof M., Chen Y., Sumi Y., Sursal T., Junger W., Brohi K., Itagaki K., Hauser C.J. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 2010, 464:104-107.
212. Zhao W., Beers D.R., Henkel J.S., Zhang W., Urushitani M., Julien J.P., Appel S.H. Extracellular mutant SOD1 induces microglial-mediated motoneuron injury. Glia 2010, 58:231-243.
213. Zhou J., Chung K., Chung J.M. Development of purinergic sensitivity in sensory neurons after peripheral nerve injury in the rat. Brain Res. 2001, 915:161-169.