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Nitric Oxide and Oxidative Damage in the CNS

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Metals and Oxidative Damage in Neurological Disorders

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Abstract

NO is synthesized by a family of enzymes known collectively as NO synthases that catalyze the reaction of L-arginine with molecular oxygen to form NO and L-citrulline. The NO synthases can be divided into 2 main groups: a) constitutive isoforms that are continuously expressed and b) inducible isoforms, the de novo synthesis of which is stimulated by cytokines or bacterial-derived lipopolysaccharide (LPS) acting alone or in synergy (Nathan, 1992; Moncada et al., 1991). Although all NO synthases catalyze the same basic reaction, they are structurally and, to a certain extent, functionally distinct enzymes encoded by separate genes (Nathan, 1992). Several important differences exist between constitutive and inducible NO synthases in terms of requirement of Ca2+ for enzyme activation, cellular localization, and perhaps most importantly in the context of this chapter, the actual amount of NO generated. These differences, discussed below, have considerable implications for both NO-dependent toxicity and the development of NO synthase inhibitors as efficacious cytoprotective drugs.

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References

  • Adamson, D. C., Wildemann, B., Sasaki, M., Glass, J. D., McArthur, J. C., Christov, V. I., Dawson, T. M., and Dawson, V. L., 1996, Immunologic NO synthase: Elevation in severe AIDS dementia and induction by HIV-1 gp41, Science 274:1917–1921.

    Article  PubMed  CAS  Google Scholar 

  • Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., and Freeman, B. A., 1990, Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide, Proc. Natl. Acad. Sci. USA 87:1620–1624.

    Article  PubMed  CAS  Google Scholar 

  • Benzing, W. C., and Mufson, E. J., 1995, Increased number of NADPH-D-positive neurons within the substantia innominata in Alzheimer’s disease, Brain Res. 670:351–355.

    Article  PubMed  CAS  Google Scholar 

  • Bereta, M., Bereta, J., Georgoff, I., Coffman, F. D., Cohen, S., and Cohen, M. C., 1994, Methylxanthines and calcium-mobilizing agents inhibit the expression of cytokine-inducible nitric oxide synthase and vascular cell adhesion molecule-1 in murine microvascular endothelial cells, Exp. Cell Res. 212:230–242.

    Article  PubMed  CAS  Google Scholar 

  • Bo, L., Dawson, T. M., Wesselingh, S., Mork, S., Choi, S., Kong, P. A., Hanley, D., and Trapp, B. D., 1994, Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brain, Ann. Neurol. 36:778–786.

    Article  PubMed  CAS  Google Scholar 

  • Boje, K. M., and Arora, P. K., 1992, Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death, Brain Res. 587:250–256.

    Article  PubMed  CAS  Google Scholar 

  • Boullerne, A. I., Petry, K. G., Meynard, M., and Geffard, M., 1995, Indirect evidence for nitric oxide involvement in multiple sclerosis by characterization of circulating antibodies directed against conjugated S-nitrosocysteine, J. Neuroimmunol. 60:117–124.

    Article  PubMed  CAS  Google Scholar 

  • Bredt, D. S., Hwang, P. M., and Snyder, S. H., 1990, Localization of nitric oxide synthase indicating a neural role for nitric oxide, Nature 347:768–770.

    Article  PubMed  CAS  Google Scholar 

  • Brosnan, C. F, Battistini, L., Raine, C. S., Dickson, D. W., Casadevall, A., and Lee, S. C., 1994, Reactive nitrogen intermediates in human neuropathology: An overview, Dev. Neurosci. 16:152–161.

    Article  PubMed  CAS  Google Scholar 

  • Brune, B., Dimmeler, S., Molina y Vedia, L., and Lapetina, E. G., 1994, Nitric oxide: A signal for ADP-ribosylation of proteins, Life Sci. 54:61–70.

    Article  PubMed  CAS  Google Scholar 

  • Cho, H. J., Xie, Q. W., Calaycay, J., Mumford, R. A., Swiderek, K. M., Lee, T. D., and Nathan, C., 1992, Calmodulin is a subunit of nitric oxide synthase from macrophages, J. Exp. Med. 176:599–604.

    Article  PubMed  CAS  Google Scholar 

  • Cross, A. H., Misko, T. P., Lin, R. F., Hickey, W. F., Trotter, J. L., and Tilton, R. G., 1994, Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice, J. Clin. Invest. 93:2684–2690.

    Article  PubMed  CAS  Google Scholar 

  • Dawson, D. A., 1994, Nitric oxide and focal cerebral ischemia: Multiplicity of actions and diverse outcome, Cerebrovasc. Brain Metabol. Rev. 6:299–324.

    CAS  Google Scholar 

  • Dawson, V. L., Dawson, T. M., Bartley, D. A., Uhl, G. R., and Snyder, S. H., 1993, Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures, J. Neurosci. 13:2651–2661.

    PubMed  CAS  Google Scholar 

  • Di Monte, D. A., Royland, J. E., Jakowec, M. W., and Langston, J. W., 1996, Role of nitric oxide in methamphetamine neurotoxicity: Protection by 7-nitroindazole, an inhibitor of neuronal nitric oxide synthase, J. Neurochem. 67:2443–2450.

    Article  PubMed  Google Scholar 

  • Dorheim, M.-A., Tracey, W. R., Pollock, J. S., and Grammas, P., 1994, Nitric oxide synthase activity is elevated in brain microvessels in Alzheimer’s disease, Biochem. Biophys. Res. Comm. 205:659–665.

    Article  PubMed  CAS  Google Scholar 

  • Ferrante, R. J., Kowall, N. W., Beal, M. F., Martin, J. B., Bird, E. D., and Richardson, E. P., 1987, Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington’s disease, J. Neuropath. Exp. Neurol. 46:12–27.

    Article  PubMed  CAS  Google Scholar 

  • Fujisawa, H., Dawson, D., Browne, S. E., Mackay, K. B., Bullock, R., and McCulloch, J., 1994, Pharmacological modification of glutamate neurotoxicity in vivo, Brain Res. 629:73–78.

    Article  Google Scholar 

  • Garthwaite, J., 1991, Glutamate, nitric oxide and cell-cell signalling in the nervous system, Trends Neurosci. 14:60–67.

    Article  PubMed  CAS  Google Scholar 

  • Gryglewski, R. J., Palmer, R. M. J., and Moncada, S., 1986, Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor, Nature 320:454–456.

    Article  PubMed  CAS  Google Scholar 

  • Hammer, B., Davis Parker, W., and Bennett, J. P., 1993, NMDA receptors increase OH radicals in vivo by using nitric oxide synthase and protein kinase C., Neuroreport 5:72–74.

    Article  PubMed  CAS  Google Scholar 

  • Hartung, H.-P, Jung, S., and Stoll, G., 1992, Inflammatory mediators in demyelinating disorders of the CNS and PNS J. Neuroimmunol. 40:197–210.

    Article  PubMed  CAS  Google Scholar 

  • Hasan, K., Heesen, B.-J., and Corbett, J. A., 1993, Inhibition of nitric oxide formation by guanidines, Eur. J. Pharmacol. 249:101–106.

    Article  PubMed  CAS  Google Scholar 

  • Hu, J., and El-Fakahany, E. E., 1993, β-Amyloid 25–35 activates nitric oxide synthase in a neuronal clone, Neuroreport 4:760–762.

    Article  PubMed  CAS  Google Scholar 

  • Huang, Z., Huang, P. L., Panahian, N., Dalkara, T., Fishman, M., and Moskowitz, M., 1994, Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase, Science 265:1883–1885.

    Article  PubMed  CAS  Google Scholar 

  • Hyman, B. T., Marzloff, K., Wenniger, J. J., Dawson, T. M., Bredt, D. S., and Snyder, S. H., 1992, Relative sparing of nitric oxide synthase-containing neurons in the hippocampal formation in Alzheimer’s disease, Ann. Neurol. 32:818–820.

    Article  PubMed  CAS  Google Scholar 

  • Iadecola, C., Xu, X., Zhang, F., El-Fakahany, E. E., and Ross, M. R., 1995a, Marked induction of calcium-independent nitric oxide synthase activity after focal cerebral ischemia, J. Cereb. Blood Flow Metabol. 15:52–59.

    Article  CAS  Google Scholar 

  • Iadecola, C., Zhang, F., and Xu, X., 1995b, Inhibition of inducible nitric oxide synthase ameliorate cerebral ischemic damage, Am. J. Physiol. 268:R286-R292.

    Google Scholar 

  • Iadecola, C., Beitz, A. J., Renno, W., Xu, X., Mayer, B., and Zhang, F., 1993, Nitric oxide synthase-containing neural processes on large cerebral arteries and cerebral microvessels, Brain Res. 606:148–155.

    Article  PubMed  CAS  Google Scholar 

  • Jaffrey, S. R., Cohen, N. A., Rouault, T., Klausner, R. D., and Snyder, S. H., 1994, The iron-responsive element binding protein: A target for synaptic actions of nitric oxide, Proc. Natl. Acad. Sci. USA 91:12994–12998.

    Article  PubMed  CAS  Google Scholar 

  • Johnson, A. W., Land, J. M., Thompson, E. J., Bolanos, J. P., Clark, J. B., and Heales, S. J. R., 1995, Evidence for increased nitric oxide production in multiple sclerosis, J. Neurol. Neurosurg. Psych. 58:107–115.

    Article  CAS  Google Scholar 

  • Kader, A., Frazzinin, V. I., Solomon, R. A., and Trifiletti, R. R., 1993, Nitric oxide production during focal cerebral ischemia in rats, Stroke 24:1709–1716.

    Article  PubMed  CAS  Google Scholar 

  • Koprowski, H., Zheng, Y. M., Heber-Katz, E., Fraser, N., Rorke, L., Fu, Z. F., Hanlon, C., and Dietzschold, B., 1993, In vivo expression of inducible nitric oxide synthase in experimentally induced neurologic diseases, Proc. Natl. Acad. Sci. USA 90:3024–3027.

    Article  PubMed  CAS  Google Scholar 

  • Kuiper, M. A., Visser, J. J., Bergmans, P. L. M., Scheltens, P., and Wolters, E. C., 1994, Decreased cerebrospinal fluid nitrate levels in Parkinson’s disease, Alzheimer’s disease and multiple system atrophy patients, J. Neurolog. Sci. 121:46–49.

    Article  CAS  Google Scholar 

  • Kwon, N. S., Stuehr, D. J., and Nathan, C. F, 1991, Inhibition of tumour cell ribonucleotide reductase by macrophage-derived nitric oxide, J. Exp. Med. 174:761–768.

    Article  PubMed  CAS  Google Scholar 

  • Lin, R. F., Lin, T.-S., Tilton, R. G., and Cross, A. H., 1993, Nitric oxide localized to spinal cords of mice with experimental allergic encephalomyelitis: an electron paramagnetic resonance study, J. Exp. Med. 178:643–648.

    Article  PubMed  CAS  Google Scholar 

  • Lipton, S. A., and Rosenberg, P. A., 1994, Excitatory amino acids as a final common pathway for neurologic disorders, N Engl. J. Med. 330:613–622.

    Article  PubMed  CAS  Google Scholar 

  • Lipton, S. A., Choi, Y.-B., Pan, Z.-H., Lei, S. Z., Chen, H.-S., Sucher, N. J., Loscaizo, J., Singel, D. J., and Stamler, J. S., 1993, A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds, Nature 364:626–632.

    Article  PubMed  CAS  Google Scholar 

  • Lockhart, B. P., Benicourt, C., Junien, J.-L., and Privat, A., 1994, Inhibitors of free radical formation fail to attenuate direct β-amyloid25–35 peptide-mediated neurotoxicity in rat hippocampal cultures, J. Neurosci. Res. 39:494–505.

    Article  PubMed  CAS  Google Scholar 

  • MacMicking, J. D., Willenborg, D. O., Weidemann, M. J., Rockett, K. A., and Cowden, W B., 1992, Elevated secretion of reactive nitrogen and oxygen intermediates by inflammatory leukocytes in hyperacute experimental autoimmune encephalomyelitis: enhancement by the soluble products of encephalitogenic T cells, J. Exp. Med. 176:303–307.

    Article  PubMed  CAS  Google Scholar 

  • Malinski, T., Bailey, F., Zhang, Z. G., and Chopp, M., 1993, Nitric oxide measured by porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion, J. Cereb. Blood Flow Metabol. 13:355–358.

    Article  CAS  Google Scholar 

  • Matsumoto, T., Nakane, M., Pollock, J. S., Kuk, J. E., and Forstermann, U., 1993, A correlation between soluble brain nitric oxide synthase and NADPH-diaphorase activity is only seen after exposure of the tissue to fixative, Neurosci. Lett. 155:61–64.

    Article  PubMed  CAS  Google Scholar 

  • McCulloch, J., Bullock, R., and Teasdale, G. M., 1991, Excitatory amino acid antagonists: Opportunities for the treatment of ischaemic brain damage in man, in: Excitatory Amino Acid Antagonists (B. S. Meldrum, ed.), Blackwell Scientific Publications, Oxford, pp. 287–326.

    Google Scholar 

  • Meda, L., Cassatella, M. A., Szendrei, G. I., Otvos, L., Baron, P., Villalba, M., Ferrari, D., and Rossi, R, 1995, Activation of microglial cells by β-amyloid protein and interferon-γ, Nature 374:647–650.

    Article  PubMed  CAS  Google Scholar 

  • Milstien, S., Sakai, N., Brew, B. J., Krieger, C., Vickers, J. H., Saito, K., and Heyes, M. R, 1994, Cerebrospinal fluid nitrite/nitrate levels in neurologic diseases, J. Neurochem. 63:1178–1180.

    Article  PubMed  CAS  Google Scholar 

  • Minc-Golomb, D., Tsarfaty, I., and Schwartz, J. R, 1994, Expression of inducible nitric oxide synthase by neurones following exposure to endotoxin and cytokine, Br. J. Pharmacol. 112:720–722.

    Article  PubMed  CAS  Google Scholar 

  • Mitrovic, B., Ignarro, L. J., Montestruque, S., Smoll, A., and Merrill, J. E., 1994, Nitric oxide as a potential pathological mechanisms in demyelination: Its differential effects on primary glial cells in vitro, Neurosci. 61:575–585.

    Article  CAS  Google Scholar 

  • Molina, J. A., Jimenez-Jimenez, R J., Navarro, J. A., Ruiz, E., Arenas, J., Cabrera-Valdivia, R, Vazquez, A., Fernandez-Calle, R, Ayuso-Peralta, L., Rabasa, M., and Bermejo, R, 1994, Plasma levels of nitrates in patients with Parkinson’s disease, J. Neurolog. Sci. 127:87–89.

    Article  CAS  Google Scholar 

  • Moncada, S., Palmer, R. M. J., and Higgs, E. A., 1991, Nitric oxide: Physiology, pathophysiology and pharmacology, Pharmacol. Rev. 43:109–142.

    PubMed  CAS  Google Scholar 

  • Moore, P. K., Wallace, P., Gaffen, Z. A., Hart, S. L., Babbedge, R. C., 1993, Characterization of the novel nitric oxide synthase inhibitor 7-nitroindazole and related indazoles: Antinociceptive and cardiovascular effects, Br. J. Pharmacol. 110:219–224.

    Article  PubMed  CAS  Google Scholar 

  • Mufson, E. J., and Brandabur, M. M., 1994, Sparing of NADPH-diaphorase striatal neurons in Parkinson’s and Alzheimer’s diseases, Neuroreport 5:705–708.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, S., Simmons, M. L., Agullo, L., Garcia, A., Feinstein, D. L., Galea, E., Reis, D. J., Minc-Golomb, D., and Schwartz, J. P., 1993, Synthesis of nitric oxide in CNS glial cells, Trends Neurosci. 16:323–328.

    Article  PubMed  CAS  Google Scholar 

  • Nagafuji, T., Sugiyama, M., and Matsui, T., 1994, Temporal profiles of Ca2+/calmodulin-dependent and -independent nitric oxide synthase activity in the rat brain microvessels following cerebral ischemia, Acta Neurochir. 60:285–288.

    CAS  Google Scholar 

  • Nathan, C., 1992, Nitric oxide as a secretory product of mammalian cells, FASEB J. 6:3051–3054.

    PubMed  CAS  Google Scholar 

  • Nguyen, T., Brunson, D., Crespi, C. I., Penman, B. W., Wishnok, J. S., and Tannenbaum, S. R., 1992, DNA damage and mutation in human cells exposed to nitric oxide in vitro, Proc. Natl. Acad. Sci. USA 89:3030–3034.

    Article  PubMed  CAS  Google Scholar 

  • Przedborski, S., Jackson-Lewis, V, Yokoyama, R., Shibata, T., Dawson, V. L., and Dawson, T. M., 1996, Role of neuronal nitric oxide in l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity, Proc. Natl. Acad. Sci. USA 93:4567–4571.

    Article  Google Scholar 

  • Olanow, C. W., 1992, An introduction to the free radical hypothesis in Parkinson’s disease, Ann. Neurol. 32:S2-S9.

    Article  Google Scholar 

  • Regidor, J., Edvinsson, L., and Divac, I., 1993, NOS neurones lie near branchings of cortical arteriolae, Neuroreport 4:112–114.

    Article  PubMed  CAS  Google Scholar 

  • Reif, D. W., and Simmons, R. D., 1990, Nitric oxide mediates iron release from ferritin, Arch. Biochem. Biophys. 283:537–541.

    Article  PubMed  CAS  Google Scholar 

  • Rossi, R, and Bianchini, E., 1996, Synergistic induction of nitric oxide by beta-amyloid and cytokines in astrocytes, Biochem. Biophys. Res. Commun. 225:474–478.

    Article  PubMed  CAS  Google Scholar 

  • Rubanyi, G. M., Ho, E. H., Cantor, E. H., Lumma, W. C., Parker Botehlo, L. H., 1991, Cytoprotective function of nitric oxide: Inactivation of superoxide radicals produced by human leukocytes, Biochem. Biophys. Res. Comm. 181:1392–1397.

    Article  PubMed  CAS  Google Scholar 

  • Schulz, J. B., Matthews, R. T., Muqit, M. M. K., Browne, S. E., and Beal, M. R, 1995, Inhibition of nitric oxide synthase by 7-nitroindazole protects against MPTP-induced neurotoxicity in mice, J. Neurochem. 64:936–939.

    Article  PubMed  CAS  Google Scholar 

  • Seiden, N., Geula, C., Hersh, L., and Mesulam, M.-M., 1994, Human striatum: chemoarchitecture of the caudate nucleus, putamen and ventral striatum in health and Alzheimer’s disease, Neuroscience 60:621–636.

    Article  Google Scholar 

  • Sheng, P., Cerruti, C., Ali, S., and Cadet, J. L., 1996, Nitric oxide is a mediator of methamphetamine (METH)-induced neurotoxicity. In vitro evidence from primary cultures of mesencephalic cells, Ann. N. Y.Acad. Sci. 801:174–186.

    Article  PubMed  CAS  Google Scholar 

  • Shergill, J. K., Cammack, R., Cooper, C. E., Cooper, J. M., Mann, V. M., and Schapira, A. H., 1996, Detection of nitrosyl complexes in human substantia nigra, in relation to Parkinson’s disease, Biochem. Biophys. Res. Commun. 228:298–305.

    Article  PubMed  CAS  Google Scholar 

  • Sherman, M. P., Griscavage, J. M., and Ignarro, L. J., 1992, Nitric oxide-mediated neuronal injury in multiple sclerosis, Med. Hyp. 39:143–146.

    Article  CAS  Google Scholar 

  • Simonian, N. A., and Coyle, J. T., 1996, Oxidative stress in neurodegenerative diseases, Ann. Rev. Pharmacol. Toxicol. 36:83–106.

    Article  CAS  Google Scholar 

  • Spencer Smith, T., Swerdlow, R. H., Parker, W. D., and Bennett, J. P., 1994, Reduction of MPP+-induced hydroxyl radical formation and nigrostriatal MPTP toxicity by inhibiting nitric oxide synthase, Neuroreport 5:2598–2600.

    Article  Google Scholar 

  • Stamler, J. R., 1994, Redox signalling: Nitrosylation and related target interactions of nitric oxide, Cell 78:931–936.

    Article  PubMed  CAS  Google Scholar 

  • Tomimoto, H., Nishimura, M., Suenaga, T., Nakamura, S., Akiguchi, I., Wakita, H., Kimura, J., and Mayer, B., 1994, Distribution of nitric oxide synthase in the human cerebral blood vessels and brain tissues, J. Cereb. Blood Flow Metabol. 14:930–938.

    Article  CAS  Google Scholar 

  • Wallis, R. A., Panizzon, K. L., Henry, D., and Wasterlain, C. G., 1993, Neuroprotection against nitric oxide injury with inhibitors of ADP-ribosylation, Neuroreport 5:245–248.

    Article  PubMed  CAS  Google Scholar 

  • Weinberg, E. D., 1992, Iron depletion: A defense against intracellular infection and neoplasia, Life Sci. 50:1289–1297.

    Article  PubMed  CAS  Google Scholar 

  • Weiss, G., Goossen, B., Doppler, W., Fuchs, D., Pantopoulos, K., Werner-Felmayer, G., Wächter, H., and Hentze, M. W., 1993, Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway, EMBO J. 12:3651–3657.

    PubMed  CAS  Google Scholar 

  • Van Dam, A.-M., Bauer, J., Man-A-Hing, W. K. H., Marquette, C., Tilders, F. J. H., and Berkenbosch, F., 1995, Appearance of inducible nitric oxide synthase in the rat central nervous system after rabies virus infection and during experimental allergic encephalomyelitis but not after peripheral administration of endotoxin, J. Neurosci. Res. 40:251–260.

    Article  PubMed  Google Scholar 

  • Vincent, S. R., and Kimura, H., 1992, Histochemical mapping of nitric oxide synthase in the rat brain, Neurosci. 46:755–784.

    Article  CAS  Google Scholar 

  • Xie, Q., and Nathan, C., 1994, The high output nitric oxide pathway: Role and regulation, J. Leukocyte Biol. 56:576–582.

    PubMed  CAS  Google Scholar 

  • Yoshida, T., Limmroth, V, Irikura, K., and Moskowitz, M. A., 1994, The NOS inhibitor, 7-nitroindazole, decreases focal infarct volume but not the response to topical acetylcholine in pial vessels, J. Cereb. Blood Flow Metabol. 14:924–929.

    Article  CAS  Google Scholar 

  • Youdim, M. B. H., Ben-Shachar, D., Eshel, G., Finberg, J. P. M., and Riederer, P., 1993, The neurotoxicity of iron and nitric oxide. Relevance to the etiology of Parkinson’s disease, Adv. Neurol. 60:259–266.

    PubMed  CAS  Google Scholar 

  • Zhang, J., Dawson, V. L., Dawson, T. M., and Snyder, S. H., 1993, Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity, Science 263:687–689.

    Article  Google Scholar 

  • Zhang, Z. G., Chopp, M., Zaloga, C., Pollock, J. S., and Forstermann, U., 1993, Cerebral endothelial nitric oxide synthase expression after focal cerebral ischemia in rats, Stroke 24:2016–2022.

    Article  PubMed  CAS  Google Scholar 

  • Zielasek, J., Jung, S., Gold, R., Liew, F. Y, Toyka, K. V, and Hartung, H. P., 1995, Administration of nitric oxide synthase inhibitors in experimental autoimmune neuritis and experimental autoimmune encephalomyelitis, J. Neuroimmunol. 58:81–88.

    Article  PubMed  CAS  Google Scholar 

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  1. Stroke Branch, NINDS, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Deborah A. Dawson

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  1. Pennsylvania State University, Hershey, Pennsylvania, USA

    James R. Connor

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Dawson, D.A. (1997). Nitric Oxide and Oxidative Damage in the CNS. In: Connor, J.R. (eds) Metals and Oxidative Damage in Neurological Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0197-2_11

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