Skip to main content
SpringerLink
Log in

TNFα in Experimental Diseases of the CNS

  • Protocol
Tumor Necrosis Factor

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 98))

Abstract

Tumor necrosis factor α (TNFα) is a crucial mediator involved in the communications between immune and nervous systems in physiological conditions, and its relevance is amplified during disease. Considered originally detrimental and a target for therapeutic intervention, recently it has also gained attention for its protective role, especially in central nervous system (CNS) confined diseases. Thus, TNFα has become the key molecule illustrating the peculiar and still not completely understood pathways by which inflammatory and immune reactions occur in the brain. Several human pathologies that lack an efficient therapy and that carry enormous social costs rely on these mechanisms. Thus, further research is needed to improve our knowledge and to allow the identification of therapeutic targets or strategies for immune-mediated inflammatory disease of the CNS in which TNFα is primarily involved. We describe here how to induce experimental autoimmune encephalomyelitis, cerebral malaria, and brain ischemia in rodents, and some protocols to analyze them. The application of innovative research strategies or original therapeutic approaches to these experimental models may be rewarding in terms of advancement in a field that is crucial for the management of many human patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Breder, C. D., Tsujimoto, M., Terano, Y., Scott, D. W., and Saper, C. B. (1993) Distribution and characterization of tumor necrosis factor-alpha-like immunoreactivity in the murine central nervous system. J. Comp. Neurol. 337, 543–567.

    Article  PubMed  CAS  Google Scholar 

  2. Lieberman, A. P., Pitha, P. M., Shin, H. S., and Shin, M. L. (1989) Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus. Proc. Natl. Acad. Sci. USA 86, 6348–6352.

    Article  PubMed  CAS  Google Scholar 

  3. Frei, K., Siepl, C., Groscurth, P., Bodmer, S., Schwerdel, C., and Fontana, A. (1987) Antigen presentation and tumor cytotoxicity by interferon-gamma-treated microglial cells. Eur. J. Immunol. 17, 1271–1278.

    Article  PubMed  CAS  Google Scholar 

  4. Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., et al. (2002) Control of synaptic strength by glial TNFalpha. Science 295, 2282–2285.

    Article  PubMed  CAS  Google Scholar 

  5. Gutierrez, E. G., Banks, W. A., and Kastin, A. J. (1993) Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J. Neuroimmunol. 47, 169–176.

    Article  PubMed  CAS  Google Scholar 

  6. Akassoglou, K., Bauer, J., Kassiotis, G., Pasparakis, M., Lassmann, H., Kollias, G., et al. (1998) Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy. Am. J. Pathol. 153, 801–813.

    Article  PubMed  CAS  Google Scholar 

  7. Arnett, H. A., Mason, J., Marino, M., Suzuki, K., Matsushima, G. K., and Ting, J. P. (2001) TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat. Neurosci. 4, 1116–1122.

    Article  PubMed  CAS  Google Scholar 

  8. Leon, L. R. (2002) Invited review: cytokine regulation of fever: studies using gene knockout mice. J. Appl. Physiol. 92, 2648–2655.

    PubMed  CAS  Google Scholar 

  9. Deboer, T., Fontana, A., and Tobler, I. (2002) Tumor necrosis factor (TNF) ligand and TNF receptor deficiency affects sleep and the sleep EEG. J. Neurophysiol. 88, 839–846.

    PubMed  CAS  Google Scholar 

  10. Ek, M., Engblom, D., Saha, S., Blomqvist, A., Jakobsson, P. J., and Ericsson-Dahlstrand, A. (2001) Inflammatory response: pathway across the blood-brain barrier. Nature 410, 430–431.

    Article  PubMed  CAS  Google Scholar 

  11. Selmaj, K. W., Farooq, M., Norton, W. T., Raine, C. S., and Brosnan, C. F. (1990) Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J. Immunol. 144, 129–135.

    PubMed  CAS  Google Scholar 

  12. Merrill, J. E. (1991) Effects of interleukin-1 and tumor necrosis factor-alpha on astrocytes, microglia, oligodendrocytes, and glial precursors in vitro. Dev. Neurosci. 13, 130–137.

    Article  PubMed  CAS  Google Scholar 

  13. Merrill, J. E., Ignarro, L. J., Sherman, M. P., Melinek, J., and Lane, T. E. (1993) Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J. Immunol. 151, 2132–2141.

    PubMed  CAS  Google Scholar 

  14. Sedgwick, J. D., Riminton, D. S., Cyster, J. G., and Korner, H. (2000) Tumor necrosis factor: a master-regulator of leukocyte movement. Immunol. Today 21, 110–113.

    Article  PubMed  CAS  Google Scholar 

  15. Selmaj, K. W. and Raine, C. S. (1988) Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann. Neurol. 23, 339–346.

    Article  PubMed  CAS  Google Scholar 

  16. Murphy, C. A., Hoek, R. M., Wiekowski, M. T., Lira, S. A., and Sedgwick, J. D. (2002) Interactions between hemopoietically derived TNFα and central nervous system-resident glial chemokines underlie initiation of autoimmune inflammation in the brain. J. Immunol. 169, 7054–7062.

    PubMed  CAS  Google Scholar 

  17. Sawada, M., Kondo, N., Suzumura, A., and Marunouchi, T. (1989) Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Res. 491, 394–397.

    Article  PubMed  CAS  Google Scholar 

  18. Osburg, B., Peiser, C., Domling, D., Schomburg, L., Ko, Y. T., Voigt, K., et al. (2002) Effect of endotoxin on expression of TNF receptors and transport of TNFalpha at the blood-brain barrier of the rat. Am. J. Physiol. Endocrinol. Metab. 283, E899–E908.

    PubMed  CAS  Google Scholar 

  19. Omari, K. M. and Dorovini-Zis, K. (2003) CD40 expressed by human brain endothelial cells regulates CD4+ T cell adhesion to endothelium. J. Neuroimmunol. 134, 166–178.

    Article  PubMed  CAS  Google Scholar 

  20. Martino, G. and Hartung, H. P. (1999) Immunopathogenesis of multiple sclerosis: the role of T cells. Curr. Opin. Neurol. 12, 309–321.

    Article  PubMed  CAS  Google Scholar 

  21. Kieseier, B. C., Storch, M. K., Archelos, J. J., Martino, G., and Hartung, H. P. (1999) Effector pathways in immune mediated central nervous system demyelination. Curr. Opin. Neurol. 12, 323–336.

    Article  PubMed  CAS  Google Scholar 

  22. Swanborg, R. H. (2001) Experimental autoimmune encephalomyelitis in the rat: lessons in T-cell immunology and autoreactivity. Immunol. Rev. 184, 129–135.

    Article  PubMed  CAS  Google Scholar 

  23. Brok, H. P., Bauer, J., Jonker, M., Blezer, E., Amor, S., Bontrop, R. E., et al. (2001) Non-human primate models of multiple sclerosis. Immunol. Rev. 183, 173–185.

    Article  PubMed  CAS  Google Scholar 

  24. Uccelli, A. Animal models of demyelination of the central nervous system. In From Basic Immunology to Immune-Mediated Demyelination (Martino, G. and Adorini, L., eds.). Springer-Verlag, Milan, Italy, 1999, pp. 233–245.

    Google Scholar 

  25. Lassmann, H. (2002) Mechanisms of demyelination and tissue destruction in multiple sclerosis. Clin. Neurol. Neurosurg. 104, 168–171.

    Article  PubMed  Google Scholar 

  26. Hofman, F. M., Hinton, D. R., Johnson, K., and Merrill, J. E. (1991) Tumor necrosis factor identified in multiple sclerosis brain. J. Exp. Med. 170, 607–612.

    Article  Google Scholar 

  27. Selmaj, K., Raine, C. S., Cannella, B., and Brosnan, C. F. (1991) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J. Clin. Invest. 87, 949–954.

    Article  PubMed  CAS  Google Scholar 

  28. Issazadeh, S., Ljungdahl, A., Hojeberg, B., Mustafa, M., and Olsson, T. (1995) Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta. J. Neuroimmunol. 61, 205–212.

    Article  PubMed  CAS  Google Scholar 

  29. Furlan, R., Martino, G., Galbiati, F., Poliani, P. L., Smiroldo, S., Bergami, A., et al. (1999) Caspase-1 regulates the inflammatory process leading to autoimmune demyelination. J. Immunol. 163, 2403–2409.

    PubMed  CAS  Google Scholar 

  30. Renno, T., Krakowski, M., Piccirillo, C., Lin, J. Y., and Owens, T. (1995) TNFalpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. Regulation by Th1 cytokines. J. Immunol. 154, 944–953.

    PubMed  CAS  Google Scholar 

  31. Probert, L., Eugster, H. P., Akassoglou, K., Bauer, J., Frei, K., Lassmann, H., et al. (2000) TNFR1 signalling is critical for the development of demyelination and the limitation of T-cell responses during immune-mediated CNS disease. Brain 123, 2005–2019.

    Article  PubMed  Google Scholar 

  32. Ruuls, S. R., Hoek, R. M., Ngo, V. N., McNeil, T., Lucian, L. A., Janatpour, M. J., et al. (2001) Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation. Immunity 15, 533–543.

    Article  PubMed  CAS  Google Scholar 

  33. Eugster, H. P., Frei, K., Bachmann, R., Bluethmann, H., Lassmann, H., and Fontana, A. (1999) Severity of symptoms and demyelination in MOG-induced EAE depends on TNFR1. Eur. J. Immunol. 29, 626–632.

    Article  PubMed  CAS  Google Scholar 

  34. Liu, J., Marino, M. W., Wong, G., Grail, D., Dunn, A., Bettadapura, J., et al. (1998) TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination. Nat. Med. 4, 78–83.

    Article  PubMed  CAS  Google Scholar 

  35. Ruddle, N. H., Bergman, C. M., McGrath, K. M., Lingenheld, E. G., Grunnet, M. L., Padula, S. J., et al. (1990) An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J. Exp. Med. 172, 1193–1200.

    Article  PubMed  CAS  Google Scholar 

  36. Selmaj, K., Raine, C. S., and Cross, A. H. (1991) Anti-tumor necrosis factor therapy abrogates autoimmune demyelination. Ann. Neurol. 30, 694–700.

    Article  PubMed  CAS  Google Scholar 

  37. Croxford, J. L., Triantaphyllopoulos, K. A., Neve, R. M., Feldmann, M., Chernajovsky, Y., and Baker, D. (2000) Gene therapy for chronic relapsing experimental allergic encephalomyelitis using cells expressing a novel soluble p75 dimeric TNF receptor. J. Immunol. 164, 2776–2781.

    PubMed  CAS  Google Scholar 

  38. The Lenercept Group. (1999) TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology 53, 457–465.

    Google Scholar 

  39. van Oosten, B. W., Barkhof, F., Truyen, L., Boringa, J. B., Bertelsmann, F. W., von Blomberg, B. M., et al. (1996) Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47, 1531–1534.

    PubMed  Google Scholar 

  40. Luhan, M. Malaria. WHO Press Office Fact Sheet 94. World Health Organization, Geneva, Switzerland, 1996, pp. 1–3.

    Google Scholar 

  41. Najera, J. A. and Hempel, J. The Burden of Malaria. WHO Press Office Publication CTD/MAL/96.10, World Health Organization, Geneva, Switzerland, 1996, pp. 1–58.

    Google Scholar 

  42. Sachs, J. and Malanay, P. (2002) The economic and social burden of malaria. Nature 415, 680–685.

    Article  PubMed  CAS  Google Scholar 

  43. Greenwood, B. M., Bradley, A. K., Greenwood, A. M., Byass, P., Jammeh, K., Marsh, K., et al. (1987) Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa. Trans. R. Soc. Trop. Med. Hyg. 81, 478–486.

    Article  PubMed  CAS  Google Scholar 

  44. Clark, I. A., Chaudhri, G., and Cowden, W. B. (1989) Roles of tumor necrosis factor in the illness and pathology of malaria. Trans. R. Soc. Trop. Med. Hyg. 83, 436–440.

    Article  PubMed  CAS  Google Scholar 

  45. Miller, L. H., Baruch, D. I., Marsh, K., and Doumbo, O. K. (2002) The pathogenic basis of malaria. Nature 415, 673–679.

    Article  PubMed  CAS  Google Scholar 

  46. Grau, G. E., Taylor, T. E., Molyneux, M. E., Wirima, J. J., Vassalli, P., Hommel, M., et al. (1989) Tumor necrosis factor and disease severity in children with falciparum malaria. N. Engl. J. Med. 320, 1586–1591.

    Article  PubMed  CAS  Google Scholar 

  47. Kwiatkowski, D., Hill, A. V. S., Sambou, I., Twumasi, P., Castracane, J., Manogue, K. R., et al. (1990) TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336, 1201–1204.

    Article  PubMed  CAS  Google Scholar 

  48. Butcher, G. A., Garland, T., Ajdukiewicz, A. B., and Clark, I. A. (1990) Serum tumor necrosis factor associated with malaria in patients in the Solomon Islands. Trans. R. Soc. Trop. Med. Hyg. 84, 658–661.

    Article  PubMed  CAS  Google Scholar 

  49. Shaffer, N., Grau, G. E., Hedberg, K., Davachi, F., Lyamba, B., Hightower, A. W., et al. (1991) Tumor necrosis factor and severe malaria. J. Infect. Dis. 163, 96–101.

    PubMed  CAS  Google Scholar 

  50. Di Perri, G., Di Perri, I. G., Monteiro, G. B., Bonora, S., Hennig, C., Cassatella, M., et al. (1995) Pentoxifylline as a supportive agent in the treatment of cerebral malaria in children. J. Infect. Dis. 171, 1317–1322.

    PubMed  Google Scholar 

  51. Manish, R., Tripathy, R., and Das, B.K. (2003) Plasma glucose and tumor necrosis factor-alpha in adult patients with severe falciparum malaria. Trop. Med. Int. Health 8, 125–128.

    Article  PubMed  CAS  Google Scholar 

  52. Sinha, B., Semmler, J., Eisenhut, T., Eigler, A., and Endres, S. (1995) Enhanced tumor necrosis factor suppression and cyclic adenosine monophosphate accumulation by combination of phosphodiesterase inhibitors and prostanoids. Eur. J. Immunol. 25, 147–153.

    Article  PubMed  CAS  Google Scholar 

  53. Lou, J., Lucas, R., and Grau, G. E. (2002) Pathogenesis of cerebral malaria: recent experimental data and possible applications in humans. Clin. Microbiol. Rev. 14, 810–820.

    Article  Google Scholar 

  54. Grau, G. E., Piguet, P. F., Vassalli, P., and Lambert, P. H. (1989) Tumor-necrosis factor and other cytokines in cerebral malaria: experimental and clinical data. Immunol. Rev. 112, 49–70.

    Article  PubMed  CAS  Google Scholar 

  55. Finley, R. W., Mackey, L. J., and Lambert, P. H. (1982) Virulent P. berghei malaria: prolonged survival and decreased cerebral pathology in T cell-deficient nude mice. J. Immunol. 129, 2213–2218.

    PubMed  CAS  Google Scholar 

  56. Grau, G. E., Piguet, P. F., Engers, H. D., Louis, J. A., Vassalli, P., and Lambert, P. H. (1986) L3T4+ T lymphocytes play a major role in the pathogensis of murine cerebral malaria. J. Immunol. 137, 2348–2354.

    PubMed  CAS  Google Scholar 

  57. Belnoue, E., Kayibanda, M., Vigario, A. M., Deschemin, J.C., van Rooijen, N., Viguier, M., et al. (2002) On the pathogenic role of brain-sequestered αβCD8+ T cells in experimental cerebral malaria. J. Immunol. 169, 6369–6375.

    PubMed  CAS  Google Scholar 

  58. Grau, G. E., Gretener, D., and Lambert, P. H. (1987) Prevention of murine cerebral malaria by low dose cyclosporin A. Immunology 61, 521–525.

    PubMed  CAS  Google Scholar 

  59. Senaldi, G., Shaklee, C. L., Guo, J., Martin, L., Boone, T., Mak, T. W., et al. (1999) Protection against the mortality associated with disease models mediated by TNF and IFN-gamma in mice lacking IFN regulatory factor-1. J. Immunol. 163, 6820–6826.

    PubMed  CAS  Google Scholar 

  60. Grau, G. E., Fajardo, L. F., Piguet, P. F., Allet, B., Lambert, P. H., and Vassalli, P. (1986) Tumor necrosis factor/cachectin as an essential mediator in murine cerebral malaria. Science 237, 1210–1212.

    Article  Google Scholar 

  61. Beutler, B., Milsark, I. W., and Cerami, A. (1986) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effects of endotoxin. Science 229, 869–871.

    Article  Google Scholar 

  62. Garcia, I., Araki, K., Miyazaki, Y., Araki, M., Juillard, P., Grau, G. E., et al. (1995) Transgenic mice expressing soluble TNFR1-IgG3 molecules are protected from lethal septic shock and cerebral malaria, and are highly sensitive to Listeria monocytogenes and Leishmania major infections. Eur. J. Immunol. 25, 2401–2407.

    Article  PubMed  CAS  Google Scholar 

  63. Lucas, R., Lou, J. N., Juillard, P., Moore, M., Bluethmann, H., and Grau, G. E. (1997) Respective role of TNF receptors in the development of experimental cerebral malaria. J. Neuroimmunol. 72, 143–148.

    Article  PubMed  Google Scholar 

  64. Grau, G. E., Pointaire, P., Piguet, P. F., Engers, H. D., Louis, J. A., Vassalli, P., et al. (1991) Late administration of monoclonal antibody to leukocyte function antigen 1 abrogates incipient murine cerebral malaria. Eur. J. Immunol. 21, 2265–2267.

    Article  PubMed  CAS  Google Scholar 

  65. Dirnagl, U., Iadecola, C., and Moskowitz, M. A. (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 22, 391–397.

    Article  PubMed  CAS  Google Scholar 

  66. Lee, J. M., Grabb, M. C., Zipfel, G. J., and Choi, D. W. (2000) Brain tissue responses to ischemia. J. Clin. Invest. 106, 723–731.

    Article  PubMed  CAS  Google Scholar 

  67. Liu, T., Clark, R. K., McDonnell, P. C., Young, P. R., White, R. F., Barone F. C., et al. (1994) Tumor necrosis factor-expression in ischemic neurons. Stroke 25, 1481–1488.

    PubMed  CAS  Google Scholar 

  68. Buttini, M., Appel, K., Sauter, A., Gebicke-Haerter, P.-J., and Boddeke, H. W. (1996) Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat. Neuroscience 71, 1–16.

    Article  PubMed  CAS  Google Scholar 

  69. Botchkina, G. I., Meistrell, M. E., III, Botchkina, I. L., and Tracey, K. J. (1997) Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia. Mol. Med. 3, 765–781.

    PubMed  CAS  Google Scholar 

  70. Sairanen, T., Carpen, O., Karjalainen-Lindsberg, M. L., Paetau, A., Turpeinen, U., Kaste, M., et al. (2001) Evolution of cerebral tumor necrosis factor-alpha production during human ischemic stroke. Stroke 32, 1750–1758.

    PubMed  CAS  Google Scholar 

  71. Meistrell, M. E., III, Botchkina, G. I., Wang, H., Di Santo, E., Cockroft, K. M., Bloom, O., et al. (1997) Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia. Shock 8, 341–348.

    Article  PubMed  Google Scholar 

  72. Dawson, D. A., Martin, D., and Hallenbeck, J. M. (1996) Inhibition of tumor necrosis factor-alpha reduces focal cerebral ischemic injury in the spontaneously hypertensive rat. Neurosci. Lett. 218, 41–44.

    Article  PubMed  CAS  Google Scholar 

  73. Navashiro, H., Martin, D., and Hallenbeck, J. M. (1997) Inhibition of tumor necrosis factor and amelioration of brain infarction in mice. J. Cereb. Blood Flow Metab. 17, 229–232.

    Article  Google Scholar 

  74. Nawashiro, H., Martin, D., and Hallenbeck, J. M. (1997) Neuroprotective effects of TNF binding protein in focal cerebral ischemia. Brain Res. 778, 265–271.

    Article  PubMed  CAS  Google Scholar 

  75. Brett, J., Gerlach, H., Nawroth, P., Steinberg, S., Godman, G., and Stern, D. (1989) Tumor necrosis factor/cachectin increases permeability of endothelial cell monolayers by a mechanism involving regulatory G proteins. J. Exp. Med. 169, 1977–1991.

    Article  PubMed  CAS  Google Scholar 

  76. Tureen, J. (1995) Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide. J. Clin. Invest. 95, 1086–1091.

    Article  PubMed  CAS  Google Scholar 

  77. Decoster, E., Vanhaesebroeck, B., Vandenabeele, P., Grooten, J., and Fiers, W. (1995) Generation and biological characterization of membrane-bound, uncleavable murine tumor necrosis factor. J. Biol. Chem. 270, 18,473–18,478.

    Article  PubMed  CAS  Google Scholar 

  78. Wong, G. H. and Goeddel, D. V. (1994) Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways. J. Immunol. 152, 1751–1755.

    PubMed  CAS  Google Scholar 

  79. Relton, J. K. and Rothwell, N. J. (1992) Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal damage in the rat. Brain Res. Bull. 29, 243–246.

    Article  PubMed  CAS  Google Scholar 

  80. Zhang, J., Dawson, V. L., Dawson, T. M., and Snyder, S. H. (1994) Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263, 687–689.

    Article  PubMed  CAS  Google Scholar 

  81. Wang, X., Yue, T. L., Barone, F. C., and Feuerstein, G. Z. (1995) Demonstration of increased endothelial-leukocyte adhesion molecule-1 mRNA expression in rat ischemic cortex. Stroke 26, 1665–1669.

    PubMed  CAS  Google Scholar 

  82. Bruce, A. J., Boling, W., Kindy, M. S., Peschon, J., Kraemer, P. J., Carpenter, M. K., et al. (1996) Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nat. Med. 2, 788–794.

    Article  PubMed  CAS  Google Scholar 

  83. Shohami, E., Ginis, I., and Hallenbeck J. M. (1999) Dual role of tumor necrosis factor alpha in brain injury. Cytokine Growth Factor Rev. 10, 119–130.

    Article  PubMed  CAS  Google Scholar 

  84. Ginsberg, M. D. and Busto, R. (1989) Rodent models of cerebral ischemia. Stroke 20, 1627–1642.

    PubMed  CAS  Google Scholar 

  85. Luvisotto, T. L. and Sutherland, G. R. Animal models of stroke. In Advances in Neurochemistry (Bachelard, H., ed.), Plenum, New York, 1997, pp. 117–144.

    Google Scholar 

  86. Chen, S. T., Hsu, C. Y., Hogan, E. L., Maricq, H., and Balentine, J. D. (1986) A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction. Stroke 17, 738–743.

    PubMed  CAS  Google Scholar 

  87. Bederson, J. B., Pitts, L. H., Germano, S. M., Nishimura, M. C., Davis, R. L., and Bartkowski, H. M. (1986) Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke 17, 1304–1308.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, San Raffaele Scientific Institute, Milan, Italy

    Roberto Furlan & Gianvito Martino

  2. Cellular and Molecular Pharmacology Section, Institute of Neuroscience, CNR, Milan, Italy

    Pia Villa

  3. Mario Negri Institute for Pharmacological Research, Milan, Italy

    Pia Villa

  4. Amgen, Thousand Oaks, CA

    Giorgio Senaldi

Authors
  1. Roberto Furlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pia Villa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giorgio Senaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gianvito Martino
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biological and Technological Research, Cancer Immunotherapy and Gene Therapy Program, San Raffaele H Scientific Institute, Milan, Italy

    Angelo Corti

  2. Mario Negri Institute for Pharmacological Research, Milan, Italy

    Pietro Ghezzi

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Humana Press Inc.

About this protocol

Cite this protocol

Furlan, R., Villa, P., Senaldi, G., Martino, G. (2004). TNFα in Experimental Diseases of the CNS. In: Corti, A., Ghezzi, P. (eds) Tumor Necrosis Factor. Methods in Molecular Medicine™, vol 98. Humana Press. https://doi.org/10.1385/1-59259-771-8:171

Download citation

  • DOI: https://doi.org/10.1385/1-59259-771-8:171

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-223-0

  • Online ISBN: 978-1-59259-771-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation