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Mechanisms of Neuroprotective Cytokines

Pleiotrophic Effects of TNFα and TGFβ on Brain Injury

  • Chapter
Cerebral Ischemia

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Experimental evidence continues to support the involvement of inflammatory/immunologic factors in the pathogenesis of ischemic brain injury. Ischemic-induced perforations in the blood-brain barrier (BBB) permit entry of humoral inflammatory mediators such as neutrophils and macrophages (Clark et al., 1994; Barone et al., 1992), whereas inherent CNS-resident microglial cells are activated following ischemic injury (Kim et al., 1995). These cells then become immunologically reactive, participating in a rapid but complex inflammatory cascade involving the release of neuroactive inflammatory mediators. These factors exert both autocrine (stimulation of further monocyte proliferation) and paracrine (effects on neuronal and endothelial cells) actions and the resulting signalling cascades have important ramifications for neurons subjected to cerebral ischemia. Soluble growth factors and cytokines are two examples of such pleiotropic signaling moieties released during inflammation that can have diverse effects on neurons under pathophysiological conditions. Both tumor necrosis factor α (TNFa) and transforming growth factor β(TGFβ) can protect neurons from metabolic, excitotoxic, and oxidative injury―modes of injury which are especially pertinent to the manifestations of ischemia. The neuroprotective mechanisms of these factors are beginning to be resolved, and involve distinct and sometimes overlapping cascades of second messenger systems leading to acute effects and long-term changes in gene expression. The further characterization of these pathways will highlight potential target sites for therapeutic pharmacological intervention, not only in stroke, but also in long term, cumulative neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS).

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References

  • Attisano, L., Wrana, J. L., Lopez-Casillas, F., and Massague, J. (1994) TGF-b receptors and actions. Biochim. Biophys. Acta. 1222, 71–80.

    Google Scholar 

  • Barger, S. W., Horster, D., Furukawa, K., Goodman, Y., Krieglstein, J., and Mattson, M. P. (1995) Tumor necrosis factors a and protect neurons against amyloid -peptide toxicity: Evidence for involvement of a KB-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc. Nat. Acad. Sci. USA 92, 9328–9332.

    Article  PubMed  CAS  Google Scholar 

  • Barone, F. C., Schmidt, D. B., Hillegass, L. M., Price, W. J., White, R. F., Feuerstein, G. Z., Clark, R. K., Lee, E. V., Griswold, D. E., and Sarau, H. M. (1992) Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia. Stroke 23, 1337–1348.

    Article  PubMed  CAS  Google Scholar 

  • Benveniste, E. N. (1992) Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am. J. Physiol. 263, C 1–C 16.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Bruce-Keller, A. J., Geddes, J. W., Knapp, P. E., McFall, R. W., Keller, J. N., Holtsberg, F. W., Steiner, S. M., Partharasy, S., and Mattson, M. P. (1999) Anti-death properties of TNF against metabolic poisening: mitochondrial stabilization by MnSOD. J. Neuroimmunol., in press.

    Google Scholar 

  • Burton, P. B. J., Queirke, P., Sorensen, C. M., Nehlsen-Cannarella, S. L., Bailey, L. L., and Knight, D. E. (1993) Growth factor expression during rat development: a comparsion of TGF-Beta3, TGF-Alpha, bFGF, PDGF and PDGF-R. Int. J. Exp. Pathol. 74, 87–96.

    Google Scholar 

  • Buttini, M., Sauter, A., and Boddeke, H. W. (1994) Induction of interleukin-n mRNA after focal cerebral ischemia in rat. Mol. Brain Res. 25, 126–134.

    Article  Google Scholar 

  • Cao, W., Carney, J. M., Duchon, A., Floyd, R. A., and Chevion, M. (1988) Oxygen free radical involvement in ischemia and reperfusion injury to brain. Neuro. Lett. 88, 233–238.

    Article  CAS  Google Scholar 

  • Chalzonitis, A. J., Kalberg, D. R., Twardzik, R. W., Morrison, W., and Kessler, A. (1992) TGF-beta has neurotrophic actions on sensory neurons in vitro and is synergistic with nerve growth fcator. Dev. Biol. 152, 121–132.

    Article  Google Scholar 

  • Chan, P. H. (1994) Oxygen radicals in focal cerebral ischemia. Brain Pathol. 4, 59–65.

    Article  PubMed  CAS  Google Scholar 

  • Chao, C. C., Hu, S., Tsang, M., Weatherbee, J., Molitor, T. W., Anderson, W. R., and Peterson, P. K. (1992a) Effects of transforming growth factor- on murine astrocyte glutamine synthetase activity: Implications in neuronal injury. J. Clin. Invest. 90, 1786–93.

    Article  PubMed  CAS  Google Scholar 

  • Chao, T. S. O., Byron, K. L., Lee, K. M., Villereal, M., and Rosner, M. R. (1992b) Activation of MAP kinases by calcium-dependent and calcium-independent pathways. J. Biol. Chem. 267, 19,876–19,883.

    Google Scholar 

  • Cheng, B., and Mattson, M. (1994) Tumor necrosis factors protect neurons against excitotoxic/metabolic insults and promote maintenance of calcium homeostasis. Neuron 12, 139–153.

    Article  PubMed  CAS  Google Scholar 

  • Clark, R. K., Lee, E. V., White, R. F., Jonak, Z. L., Feuerstein, G. Z., and Barone, F. C. (1994) Reperfusion following focal stroke hastens inflammation and resolution of ischemic injured tissue. Brain Res. Bull. 35, 387–392.

    Article  CAS  Google Scholar 

  • Cox, D. A. (1995) Transforming growth factor-beta 3. Cell Biol. Int. 19, 357–371.

    Google Scholar 

  • Cuvillier, O., Pirianiv, G., Kleuser, B., Vanek, P. G., Coso, O. A., Gutkind, J. S., and Spiegel, S. (1996) Supression of ceramide-mediated programmed cell death by sphingosine-l-phosphate. Nature 381, 800–803.

    Google Scholar 

  • Denhez, F., Lafyatis, R., Kondaiah, P., Roberts, A. B., and Sporn, M. B. (1990) Cloning by polymerase chain reaction of a new mouse TGF-bata, mTGF-beta 3. Growth Fact. 3, 139–146.

    Google Scholar 

  • Derynck, R. (1992) The physiology of transforming growth factor-alpha. Adv. Cancer Res. 58, 27–52.

    Google Scholar 

  • Ellerby, L. M., Ellerby, H. M., Park, S. M., Holleran, A. L., Murphy, A. N., Fiskum, G., Kane, D. J., Testa, M. P., Kayalar, C., and Bredesen, D. E. (1996) Shift of the cellular oxidation-reduction potential in neural cells expressing Bcl-2. J. Neurochem. 67, 1259–1267.

    Google Scholar 

  • Finch, C. E., Laping, N. J., Morgan, T. E., Nichols, N. R., and Pasinetti, G. M. (1993) TGF-β1 is an organizer of responses to neurodegeneration. J. Cell. Biochem. 53, 314–22.

    Google Scholar 

  • Fontana, A., Constam, D. B., Frei, K., Malipiero, U., and Pfister, H. W. (1992) Modulation of the immune response by transforming growth factor beta. Int. Arch. Immunol. 99, 1–7.

    Google Scholar 

  • Fowlis, D. J., Flanders, K. C., Diffie, E., Balmain, A., and Akhurst, R. J. (1992) Discordant TGF-beta1 mRNA and protein localization during chemical carcinogenesis of the skin. Cell Growth Differ. 3, 351–355.

    Google Scholar 

  • Gadient, R. A., Cron, K. C., and Otten, U. (1990) Interleukin-1 and tumor necrosis factor-alpha synergistically stimulate nerve growth factor (NGF) release from cultured rat astrcytes. Neurosci. Lett. 117, 335–340.

    Article  PubMed  CAS  Google Scholar 

  • Garcia, I., Martinou, I., Tsujimoto, Y., and Martinou, J. C. (1992) Prevention of programmed cell death of sympathetic neurons by bc1–2 proto-oncogene. Science 258, 302–304.

    Google Scholar 

  • Gilbert, R. S., and Herschman, H. R. (1993) Transforming growth factor beta differentially modulates the inducible nitric oxide synthase gene in distinct cell types. Biochem. Biophys. Res. Commun. 195, 380–384.

    Article  PubMed  CAS  Google Scholar 

  • Gomez, N., and Cohen, P. (1991) Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Nature 353, 170–173.

    Article  PubMed  CAS  Google Scholar 

  • Goodman, Y., and Mattson, M. P. (1996) Ceramide protects hippocampal neurons against excitotoxic and oxidative insults, and amyloid β-peptide toxicity. J. Neurochem. 66, 869–872.

    Article  PubMed  CAS  Google Scholar 

  • Goossens, V., Grooten, J., De Vos, K., and Fiers, W. (1995) Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity. Proc. Natl. Acad. Sci. USA 92, 8115–8119.

    Google Scholar 

  • Graves, J. D., Campbell, J. S., and Krebs, E. G. (1995) Protein serine/threonine kinases of the MAPK cascade. Ann. N. Y. Acad. Sci. 476, 330–342.

    Google Scholar 

  • Gross, C. E., Bednar, M. M., Howard, D. B., and Sporn, M. B. (1993) Transforming growth factor-1 reduces infarct size after experimental cerebral ischemia in a rabbit model. Stroke 24, 558–562.

    Article  PubMed  CAS  Google Scholar 

  • Henrick-Noack, P., Prehn, J. H. M., and Kreiglestein, J. (1996) TGF-1 protects hippocampal neurons against degeneration caused by transient global ischemia. Doseresponse relationship and potential neuronrpotective mechanisms. Stroke 27, 1609–1615.

    Article  Google Scholar 

  • Hockenbery, D. M., Oltvai, Z. N., Xiao-Ming, Y., Milliman, C. L., and Korsmeyer, S. J. (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75, 241–251.

    Article  PubMed  CAS  Google Scholar 

  • Howe, L. R., Leevers, S. J., Gomez, N., Nakieiny, S., Cohen, P., and Marshall, C. J. (1992) Activation of the MAP kinase pathway by the protein kinase raf. Cell 71, 335–342.

    Google Scholar 

  • Hsu, H., Xiong, J., and Goeddel, D. V. (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kB activation. Cell 81, 495–504.

    Google Scholar 

  • Hu, S., Sheng, W. S., Peterson, P. K., and Chao, C. C. (1995) Cytokine modulation of murine microglial cell superoxide production. Glia 13, 45–50.

    Article  PubMed  CAS  Google Scholar 

  • Hunter, K. E., Sporn, M. B., and Davies, A. M. (1993) TGF-betas inhibit mitogen-stimulated proliferationof astrocytes. Glia 7, 203–211.

    Google Scholar 

  • Jaattela, M. (1991) Biological activities and mechanisms of action of tumor necrosis factor alpha⁄cachectin. Lab. Invest. 64, 724–742.

    PubMed  CAS  Google Scholar 

  • Jennings, J. C., Mohan, S., Linkhart, T. A., Widstrom, R., and Baylink, D. (1988) Comparison of the biological actions of TGF-1 and TGF-2: differential activity in endothelial cells. Exp. Cell Res. 203, 499–503.

    Google Scholar 

  • Kalthoff, H., Roeder, C., Brockhaust, M., Thiele, H.-G., and Schmiegel, W. (1993) Tumor necrosis factor (TNF) up regulates the expression of p75 but not p55 TNF receptors, and both receptors mediate, independently of each other, up-regulation of transforming growth factor a and epidermal growth factor mRNA. J. Biol. Chem. 268, 2762–2766.

    PubMed  CAS  Google Scholar 

  • Kane, D. J., Ord, T., Anton, R., and Bredesen, D. E. (1995) Expression of bc1–2 inhibits necrotic neural cell death. J. Neurosci. 40, 269–275.

    Google Scholar 

  • Kapas, L., Hong, L., Cady, A., Opp, M., Postlethwaite, A., Seyer, J., and Krueger, J. (1992) Somnogenic, pyrogenic, and anorectic activities of tumor necrosis factor-a and TNF-a fragments. Am. J. Physiol. 263, R708–R715.

    Google Scholar 

  • Kim, J. S. (1996) Cytokines and adhesion molecules in stroke and related diseases. J. Neurol. Sci. 137, 69–78.

    Article  PubMed  CAS  Google Scholar 

  • Kim, J. S., Gautam, S. C., Chopp, M., Zaloga, C., Jones, M. L., Ward, P. A., and Welch, K. M. A. (1995) Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 after focal cerebral ischemia in the rat. J. Neuroimmunol. 56, 127–134.

    Article  PubMed  CAS  Google Scholar 

  • Kinouchi, K., Brown, G., Pasternak, G., and Donner, D. B. (1991) Identification and characterization of receptors for tumor necrosis factor alpha in the brain. Biochem. Biophys. Res. Commun. 181, 1532–1538.

    Article  PubMed  CAS  Google Scholar 

  • Klempt, N. D., Sirimanne, E., and Gunn, A. J. (1992) Hypoxia-ischemia induces transforming growth factor beta 1 mRNA in th infant rat brain. Mol. Brain Res. 13, 93–101.

    Article  PubMed  CAS  Google Scholar 

  • Knckey, N. W., Finch, O., Palm, D. E., Primiano, M. J., Johanson, C. E., Flanders, K. C., and Thompson, N. L. (1996) Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemia. Mol. Brain Res. 40, 1–14.

    Google Scholar 

  • Kolesnick, R., and Golde, D. W. (1994) The sphingomyelin pathway in TNF and I1–1 signaling. Cell 77, 325–328.

    Google Scholar 

  • Kolodziejczyk, S. M., and Hall, B. K. (1996) Signal transduction and TGF-beta superfamily receptors. Biochem. Cell Biol. 74, 299–314.

    Article  PubMed  CAS  Google Scholar 

  • Krupinski, J., Kumar, P., Kumar, S., Path, F R. C., and Kaluza, J. (1996) Increased expression of TGF-1 in brain tissue after ischemic stroke in humans. Stroke 27, 852–857.

    Google Scholar 

  • Kyriakis, J. M., App, H., Zhang, X. F., Banerjee, P., Brautigan, D. L., Rapp, U. R., and Avruch, J. (1992) Raf-1 activates MAP kinase-kinase. Nature 358, 417–421.

    Article  PubMed  CAS  Google Scholar 

  • Lafon-Cazal, M., Pietri, S., Cuicasi, M., and Bockaert, J. (1993) NMDA-dependent superoxide production and neurotoxicity. Lett. Nat. 364, 535–537.

    Article  CAS  Google Scholar 

  • Le, J., and Vilcek, J. (1987) Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab. Invest. 56, 234–248.

    PubMed  CAS  Google Scholar 

  • Lefebvre, P. P., Staecker, H., Weber, T., Van de Water, T. R., Rogister, B., and Moonen, G. (1991) TGF-betal modulates bFGF recpetor message expression in cultured adult auditory neurons. NeuroReport 2, 305–308.

    Google Scholar 

  • Lehrmann, E., Kiefer, R., Finsen, B., Diemer, N. H., Zimmer, J., and Hartung, H. (1995) Cytokines in cerebral ischemia: Expresion of tansforming growth factor beta-1 mRNA in the postischemic adult rat hippocampus. Exp. Neurol. 131, 114–123.

    Google Scholar 

  • Lewis, M., Tartaglia, L. A., Lee, A., Bennett, G. L., Rice, G. C., Wang, G. H. W., Chen, E. Y., and Goeddel, D. V. (1991) Cloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific. Proc. Natl. Acad. Sci. USA 88, 2830–2834.

    Article  PubMed  CAS  Google Scholar 

  • Lindholm, D., Castren, E., Keifer, R., Zafra, F., and Theonen, H. (1992) TGF-beta 1 in tha rat brain: increase afterinjury and inhibition of astrocyte proliferation. Brain Res. 117, 395–400.

    Google Scholar 

  • Liu, T., Clark, R. K., McConnell, P. C., Young, P. R., White, R. F., Barone, F. C., and Feuerstein, G. Z. (1994) Tumor necrosis factor in ischemic neurons. Stroke 25, 1481–1488.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Z.-G., Hsu, H., Goeddel, D. V., and Karin, M. (1996) Dissection of TNF receptor 1 effector functions: JNK activation is activation prevents cell death. Cell 87, 565–576.

    Google Scholar 

  • Lloyd, E. D., and Wooten, M. W. (1992) pp42⁄44 MAP kinase is a component of the neurogenic pathway utilized by nerve growth factor in PC12 cells. J. Neurochem. 59, 1099–1109.

    Google Scholar 

  • Lodge, P. A., and Sriram, S. (1996) Regulation of microglial activation by TGF-, I1–10, and CSF-1. J. Leuk. Biol. 60, 502–508.

    CAS  Google Scholar 

  • Lopez-Casillas, F., Wrana, J. L., and Massague, J. (1993) Betaglycan presents ligand to the TGF beta signalling receptor. Cell 73, 1435–1444.

    Article  PubMed  CAS  Google Scholar 

  • Marquardt, H., Hunkapiller, M. W., Hood, L. E., and Todaro, G. J. (1984) Rat transforming growth factor type 1: structure and relation to epidermal growth factor. cience 223, 1079–1082.

    CAS  Google Scholar 

  • Massague, J. (1987) The TGFb family of growth and differentiation factors. Cell 49, 437–438.

    Article  PubMed  CAS  Google Scholar 

  • Mattson, M., Cheng, B., Baldwin, S., Smith-Swintosky, V., Keller, J., Geddes, J., Scheff, S., and Christakos, S. (1994a) Brain injury and tumor necrosis factors induce expression of calbidin D-28 in astrocytes: evidence for a a cytoprotective response. J. Neurosci. Res. 42, 357–370.

    Google Scholar 

  • Mattson, M. P., Barger, S. W., Begeley, J., and Mark, R. J. (1994b) Calcium, free radicals, and excitotoxic neuronal death in primary cell culture. Meth. Cell Biol.46, 187–216.

    Article  Google Scholar 

  • McNeill, H., Williams, C., Guan, J., Dragunow, M., Lawlor, P., Sirimanne, E., Nikolics, K., and Gluckman, P. (1994) Neuronal rescue with transforming growth factor-β1 after hypoxicischemic brain injury. Neuroreport 5, 901–904.

    Google Scholar 

  • Merill, J. E., and Zimmermann, R. P. (1991) Natural and induced cytotoxicity of oligodendrocytes by microglia inhibitable by TGF-. Glia 4, 327–331.

    Article  Google Scholar 

  • Merrill, J. (1992) Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain development: normal and pathological. Dev. Neurosci. 14, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Merwin, J. R., Anderson, J., Kocher, 0., van Itallia, C., and Madri, J. C. (1990) TGF-beta midulates extracellular matrix organization and cell junctional complex formation during in vitro angiogenesis. J. Cell. Physiol. 142, 117–128.

    Google Scholar 

  • Minami, M., Kuraishi, Y., and Satoh, M. (1991) Effects of Kainic acid on messenger RNA levels of IL-1B, IL-6, TNFa and LIF in the rat brain. Biochem. Biophys. Res. Commun. 176, 593–598.

    Article  PubMed  CAS  Google Scholar 

  • Miyazono, K. (1997) TGF-b receptors and signal transduction. Int. J. Hematol. 65, 97–104.

    Article  PubMed  CAS  Google Scholar 

  • Mizuno, T., Sawada, M., Suzumura, A., and Marunouchi, T. (1994) Expression of cytokines during glial differentiation. Brain Res. 656, 141–146.

    Article  PubMed  CAS  Google Scholar 

  • Newfield, S. J., Chartoff, E. H., Graff, J. M., Melton, D. A., and Gelbart, W. (1996) Mothers against dpp encodes a conserved cytoplasmic protein required in DPP⁄TGF-beta responsive cells. Development 122, 2099–2108.

    Google Scholar 

  • Nishida, E., and Gotoh, Y. (1993) The MAP kinase cascade is essential for diverse signal transduction pathways. TIBS 18, 128–131.

    PubMed  CAS  Google Scholar 

  • Paul, N. L., and Ruddle, N. H. (1988) Lymphotoxin. Ann. Rev. Immunol. 6, 407–438.

    Article  CAS  Google Scholar 

  • Pennica, D., Nedwin, G. E., Hayflick, J. S., Seeberg, P. H., Derynck, R., Palladino, M. A., Kohr, W. J., Aggarwal, B. B., and Goeddle, D. V. (1984) Human tunor necrosis factor: precursor structure, expression, expression and homology to lymphotoxin. Nature 312, 724–729.

    Google Scholar 

  • Plouet, J., and Gospodarowicz, D. (1989) Transforming growth factor Beta-1 positively modulates the bioactivity of fibroblast growth factor on corneal endothelial cells. J. Cell. Physiol. 141, 392–399.

    Article  PubMed  CAS  Google Scholar 

  • Ponzoni, M., Casalaro, A., Lanciotti, M., Montaldo, P. G., and Cornaglia-Ferraris, P. (1992) The combination of gamma interferon and tumor necrosis factor causes a rapid and extensive differentiation of human neuroblastoma cells. Cancer Res. 52, 931–939.

    PubMed  CAS  Google Scholar 

  • Prehn, H. M. J., Peruche, B., Unsicker, K., and Krieglstein, J. (1993) Isoform specific effects of transforming growth factors-β on degeneration of primary neuronal cultures induced by cytotoxic hypoxia or glutamate. J. Neurochem. 60, 1665–1672.

    Google Scholar 

  • Prehn, J. H. M. (1996) Marked diversity in the action of growth factors on N-methyl-Daspartate-induced neuronal degeneration. Eur. J. Pharm. 306, 81–88.

    Article  CAS  Google Scholar 

  • Prehn, J. H. M., Backhaub, C., and Krieglstein, J. (1993) Transforming growth factor-1 prevents glutamate neurotoxicity in rat neocortical cultures and protects mouse from ischemic injury in vivo. J. Cereb. Blood Flow Metab. 13, 521–525.

    Article  PubMed  CAS  Google Scholar 

  • Prehn, J. H. M., Bindokas, V. P., Marcuccilli, C. J., Krajewski, D., Reed, J. C., and MIller, R. J. (1994) Regulation of neuronal bcl-2 expression and calcium homeostasis by transforming growth factor -beta confers wide-ranging protection on rat hippocampal neurons. Proc. Nat. Acad. Sci. USA 91, 12599–12603.

    Google Scholar 

  • Reimann, T., Hempel, U., Krautwald, S., Axmann, A., Schiebe, R., Siedel, D., and Wenzel K. (1997) Transforming growth factor beta induces activation of Ras, Raf-1, MEK, and MAPK in rat hepatic stellate cells. FEBS Lett. 403, 57–60.

    Article  PubMed  CAS  Google Scholar 

  • Reiner, G., Oliver, M., Skamene, E., and Radzioch, D. (1994) Induction of TNF gene expression by lipoprotein lipase requires protein kinase C avtivation. J. Lipid Res. 35, 1413–1421.

    PubMed  CAS  Google Scholar 

  • Roberts, A. B., Kim, J. S., Kondaiah, P., Jakowlew, S. B., Denhez, F., Glick, A. B., Geiser, A. G., Watanbe, S., Noma, T., Lechleider, R., and Sporn, M. B. (1990) Transcriptional control of expression of TGF-beta. Ann. NYAcad. Sci. 593, 43–50.

    Google Scholar 

  • Rothe, M., Pan, M.-G., Henzel, W. J., Ayres, T. M., and Goeddel, D. V. (1995a) The TNFR2-TRAF signaling complex contains two novel proteins related to baculorival inhibitor of apoptosis proteins. Cell 83, 1243–1252.

    Article  PubMed  CAS  Google Scholar 

  • Rothe, M., Sarma, V., Dixit, V. M., and Goeddel, D. V. (1995b) TRAF2-mediated activation of NF-kB by TNF receptor 2 and cd40. Science 269, 1424–1427.

    Article  PubMed  CAS  Google Scholar 

  • Schreck, R., Albermann, K., and Baeuerle, P. (1992) Nuclear factor kB: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Rad. Res. Comms. 17, 221–237.

    CAS  Google Scholar 

  • Schulz, J. B., Henshaw, D. R., Siwek, D., Jenkins, B. G., Ferrante, R. J., Cipolloni, P. B., Kowall, N. W., Rosen, B. R., and Beal, M. F. (1995) Involvement of free radicals in excitotoxicity in vivo. J. Neurochem. 64, 2239–2247.

    Article  PubMed  CAS  Google Scholar 

  • Shibuya, H., Yamaguchi, K., Shirakbe, K., Tonegawa, A., Gotoh, Y., Ueno, N., Irie, K., Nishida, E., and Matsumoto, K. (1996) TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science 272, 1179–1182.

    Google Scholar 

  • Smith, C. A., Farrah, T., and Goodwin, R. G. (1994) The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 76, 959–962. Soliven, B., and Albert, J. (1991) Tumor necrosis factor inhibits K+ current exporession in cultured sympathetic neurons. J. Neurochem. 58, 1073–1078.

    Google Scholar 

  • Soliven, B., and Albert, J. (1992) Tumor necrosis factor modulates Ca2+ currents in cultured sympathetic neurons. J. Neurosci. 12, 2665–2671.

    PubMed  CAS  Google Scholar 

  • Suzumura, A., Sawada, M., Yamamoto, H., and Marunouchi, T. (1993) TGF supresses activation and proliferation of microglia in vitro. J. Immunol. 151, 2150–2158.

    PubMed  CAS  Google Scholar 

  • Szaflarski, J., Burtrum, D., and Silverstein, F. S. (1995) Cerebral hypoxia stimulates cytokine gene expression in perinatal rats. Stroke 26, 1093–1100.

    Google Scholar 

  • Tancredi, V., D’Arcangelo, G., et.al. (1992) Tumor necrosis factor alters synaptic transmission in rat hi0camoal slices. Neurosci. Lett. 146. 176–178.

    CAS  Google Scholar 

  • Tartaglia, L. A., and Goeddal, D. (1992) Two TNF receptors. Immunol. Today 13, 151.

    Article  PubMed  CAS  Google Scholar 

  • Tartaglia, L. A., Pennica, D., and Goeddel, D. V. (1993) Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor. J. Biol. Chem. 268, 18,542–18,548.

    Google Scholar 

  • Taupin, V., Toulmond, S., Serrano, A., Benavides, J., and Zavala, F. (1993) Increase in IL6, IL-1 and TNF levels in rat brain following traumatic lesion. J. Neuroimmunol. 42, 177–186.

    Google Scholar 

  • Tchelingerian, J., Quinonero, J., Booss, J., and Jacque, C. (1993) Localization of TNFa and IL-la immunoreactivities in striatal neurons after surgical injury to the hippocampus. Neuron 10, 213–224.

    Google Scholar 

  • ten Dijke, P., Hansen, P., Iwata, K. K., Pieler, C., and Foulkes, J. G. (1988) Identification of another member of the transforming growth fcator type b gene family. Proc. Natl. Acad. Sci. USA 85, 4715–4719.

    Google Scholar 

  • Terai, K., Matsuo, A., McGeer, E. G., and McGeer, P. L. (1996) Enhancement of immunoreactivity for NF-kappa B in human cerebral infarctions. Brain Res. 739, 343–349.

    Article  PubMed  CAS  Google Scholar 

  • Thoma, B., Grell, M., Pfizenmaier, K., and Scheurich, P. (1990) Identification of a 60-kD tumor necrosis factor (TNF) receptor as the major signal transducing component in TNF responses. J. Exp. Med. 172, 1019–1023.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, S. M., DeMarco, M., D’Arcangelo, G., Halegoua, S., and Brugge, J. S. (1992) Ras is essential for nerve growth factor-and phorbol ester-induced tyrosine phosphorylation of MAP kinases. Cell 68, 1031–1040.

    Article  PubMed  CAS  Google Scholar 

  • Thompson, N. L., Flanders, K. C., Smith, J. M., Ellingsworth, L. R., Roberts, A. B., and Sporn, M. B. (1989) Expression of TGF-beta 1 in specific cells and tissues of adult and neonatal mice. J. Cell Biol. 661–669.

    Google Scholar 

  • Toru-Delbauffe, D., Baghdassarian-Chalaye, D., Gavaret, J. M., Courtin, F., and Pierre, M. (1990) Effects of TGF-beta 1 on astroglial cells in culture. J. Neurochem. 54, 1056–1061.

    Article  PubMed  CAS  Google Scholar 

  • Ulich, T. R., Songemi, Y., Guo, K., Yi, E. S., Remick, D., and del Castillo, J. (1991) Intrathecal injection of endotoxin and cytokines. Am. J. Pathol. 138, 1099–1101.

    Google Scholar 

  • Unsicker, K., Grothe, C., Westermann, R., and Wewetzer, K. (1992) Cytokines in neurol regeneration. Curr. Opin. Neurobiol. 2, 671–678.

    Article  PubMed  CAS  Google Scholar 

  • Unsicker, K., Meier, C., Krieglstein, K., Sartor, B. M., and Flanders, K. C. (1996) Expression, localization, and function of transforming growth factor-s in embryonic chick spinal cord, hindbrain, and dorsal root ganglia. J. Neurobiol. 29, 262–276.

    Article  PubMed  CAS  Google Scholar 

  • Wolvers, D. A., Marquette, C., Berkenbosch, F., and Haour, R(1993) Tumor necrosis factor alpha: specific binding sites in the rodent brain and pituitary gland. Eur. Cytokine Netw. 4, 377–381.

    Google Scholar 

  • Wrana, J. L., Attisano, L., Wieser, R., Ventura, F., and Massague, J. (1994) Mechanism of activation of the TGF-B receptor. Nature 370, 341–347.

    Google Scholar 

  • Zafra, F., Lindholm, D., Castren, E., Hartika, J., and Threonen, H. (1992) Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of rat hippocampal neurons and astrocytes. J. Neurosci. 12, 4793–4799.

    Google Scholar 

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Authors
  1. Annadora J. Bruce-Keller
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  2. Mark P. Mattson
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Editors and Affiliations

  1. Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada

    Wolfgang Walz

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© 1999 Springer Science+Business Media New York

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Bruce-Keller, A.J., Mattson, M.P. (1999). Mechanisms of Neuroprotective Cytokines. In: Walz, W. (eds) Cerebral Ischemia. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-479-5_6

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  • DOI: https://doi.org/10.1007/978-1-59259-479-5_6

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-4735-5

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