Skip to main content
SpringerLink
Log in
Book cover

Cerebral Ischemia pp 105–123Cite as

Oxygen Radicals

  • Chapter

  • 187 Accesses

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

Abstract

Oxygen free radicals, or oxidants, have been implicated in the development of many neurological disorders and brain dysfunctions (Chan, 1988, 1992; Chan et al., 1992; Hall and Braughler, 1989; Kontos, 1985; Siesjö et al., 1989). A role that oxygen free radicals may play in brain injury appears to involve reperfusion after cerebral ischemia. In either global or focal cerebral ischemia, cerebral blood flow (CBF) is significantly reduced in the brain regions that are supplied with oxygen by the occluded vessel. Reoxygenation during reperfusion provides oxygen to sustain neuronal viability and also provides oxygen as a substrate for numerous enzymatic oxidation reactions that produce reactive oxidants. In addition, reflow following occlusion often causes an increase in oxygen to levels that cannot be utilized by mitochondria under normal physiological flow conditions (Fig. 1). It has been demonstrated that about 2–5% of the electron nitric oxide (NO) flow in isolated brain mitochondria produces superoxide (O2 ·−) and hydrogen (H2O2) (Boveris and Chance, 1973). These constantly produced oxygen radicals are scavenged respectively by superoxide dismutases (SODs), glutathione peroxidases (GSHPx), and catalase. Other antioxidants, including glutathione (GSH), ascorbic acid, and vitamin E are also likely to be involved in the detoxification of free radicals. During reperfusion, it is likely that these antioxidative defense mechanisms are perturbed as a result of the overproduction of oxygen radicals, inactivation of detoxification systems, consumption of antioxidants, and the failure to adequately replenish them in the ischemic brain tissue.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Armstead, W. M., Mirro, R., Thelin, 0. P., Shibata, M., Zuckerman, S. L., Shanklin, D. R., Busija, D. W., and Leffler, C. W. (1992) Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets. Stroke 23, 755–762.

    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.

    Google Scholar 

  • Beckman, J. S., Carson, M., Smith, C. C., and Koppenol, W. H. (1993) ALS, SOD and peroxynitrite. Nature 364, 584 (Letter).

    Google Scholar 

  • Bindokas, V. P., Jordán, J., Lee, C. C., and Miller, R. J. (1996) Superoxide production in rat hippocampal neurons: Selective imaging with hydroethidine. J. Neurosci. 16, 1324–1336.

    PubMed  CAS  Google Scholar 

  • Boveris, A., and Chance, B. (1973) The mitochondrial generation of hydrogen peroxide. Biochem. J. 134, 707–716.

    PubMed  CAS  Google Scholar 

  • Carney, J. M., Starke-Reed, P. E., Oliver, C. N., Landum, R. W., Cheng, M. S., Wu, J. F., and Floyd, R. A. (1991) Reversal of age-related increase in brain protein oxidation decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-L-phenylnitrone. Proc. Natl. Acad. Sci. USA 88, 3633–3636.

    Article  PubMed  CAS  Google Scholar 

  • Cathcart, R., Schwiers, E., Saul, R. L., and Ames, B. N. (1984) Thymine glycol and thymidine glycol in human and rat urine: a possible assay for oxidative DNA damage. Proc. Natl. Acad. Sci. USA 81, 5633–5637.

    Article  PubMed  CAS  Google Scholar 

  • Cerchiari, E. L., Hoel, T. M., Safar, P., and Sclabassi, R. J. (1987) Protective effects of combined superoxide dismutase and deferoxamine on recovery of cerebral blood flow and function after cardiac arrest in dogs. Stroke 18, 869–878.

    Google Scholar 

  • Chan, P. H. (1992) Antioxidant-dependent amelioration of brain injury: Role of CuZnsuperoxide dismutase. J. Neurotrauma. 9 (Suppl. 2), S417–S423.

    Google Scholar 

  • Chan, P. H. (1988) The role of oxygen radicals in brain injury and edema, in Cellular Antioxidant Defense Mechanisms. (Chow C. K., ed.), CRC Press, Boca Raton, FL, pp. 89–109.

    Google Scholar 

  • Chan, P. H., Chen, S., Imaizumi, S., Chu, L., Kelleher, J. A., Gregory, G. A., and Chan, T. (1992 ) New insights into the role of oxygen radicals in cerebral ischemia, in Advances in Neurochemistry, vol. 7: Neurochemical Correlates of Cerebral Ischemia. (Bazan N. G., Braquet P., and Ginsberg M. eds.), Plenum Press, New York, pp. 277–294.

    Google Scholar 

  • Chan, P. H., Chu, L., Chen, S. F., Carlson, E. J., and Epstein, C. J. (1990) Reduced neurotoxicity in transgenic mice overexpressing human copper-zinc superoxide dismutase. Stroke 21, 80–82.

    Google Scholar 

  • Chan, P. H., Epstein, C. J., Kinouchi, H., Imaizumi, S., Carlson, E., and Chen, S. F. (1993a) Role of superoxide dismutase in ischemic brain injury: reduction of edema and infarction in transgenic mice following focal cerebral ischemia. Prog. Brain Res. 96, 97–104.

    Google Scholar 

  • Chan, P. H., Kamii, H., Yang, G., Gafni, J., Epstein, C. J., Carlson, E., and Reola, L. (1993b) Brain infarction is not reduced in SOD-1 transgenic mice after a permanent focal cerebral ischemia. Neuroreport 5, 293–296.

    Google Scholar 

  • Chan, P. H., Longar, S., and Fishman, R. A. (1987) Protective effects of liposomeentrapped superoxide dismutase on post-traumatic brain edema. Ann. Neurol. 21, 540–547.

    Google Scholar 

  • Chan, P. H., Yang, G. Y., Chen, S. F., Carlson, E., and Epstein, C. J. (1991) Cold-induced brain edema and infarction are reduced in transgenic mice overexpressing CuZnsuperoxide dismutase. Ann. Neurol. 29, 482–486.

    Google Scholar 

  • Chen, J., Graham, S. H., Chan, P. H., Lan, J., Zhou, R. L., and Simon, R. P. (1995) bcl-2 is expressed in neurons that survive focal ischemia in the rat. Neuroreport 6, 394–398.

    Google Scholar 

  • Conquet, F., Bashir, Z. I., Davies, C. H., Daniel, H., Ferraguti, F., Bordi, F., Franz-Bacon, K., Reggiani, A., Matarese, V., and Conde, F. (1994) Motor deficit and impairment of synaptic plasticity in mice lacking mGluRl. Nature 372, 237–243.

    Article  PubMed  CAS  Google Scholar 

  • Crumrine, R. C., Thomas, A. L., and Morgan, P. F. (1994) Attenuation of p53 expression protects against focal ischemic damage in transgenic mice. J. Cereb. Blood Flow Metab. 14, 887–891.

    Article  PubMed  CAS  Google Scholar 

  • Dawson, T. M., Dawson, V. L., and Snyder, S. H. (1992) A novel neuronal messenger molecule in brain: the free radical, nitric oxide. Ann. Neurol. 32, 297–311.

    Article  PubMed  CAS  Google Scholar 

  • Dawson, V. L., Dawson, T. M., Bartely, 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.

    Google Scholar 

  • Dugan. L. L., Sensi, S. L., Canzoniero, L. M. T., Handran, S. C., Rothman, S. M., Lin, T.-S., Goldberg, M. P., and Choi, D. W. (1995) Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate. J. Neurosci. 15, 6377–6388.

    Google Scholar 

  • Edwards, R. H., Rutter, W. J., and Hanahan D. (1989) Directed expression of NGF to pancreatic cells in transgenic mice leads to selective hyperinervation of the islets. Cell 58, 161–170.

    Google Scholar 

  • Epstein, C. J., Avraham, K. B., Lovett, M., Smith, S., Elroy-Stein, O., Rotman, G., Bry, C., and Groner, Y. (1987) Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome. Proc. Natl. Acad. Sci. USA 84, 8044–8048.

    Article  PubMed  CAS  Google Scholar 

  • Epstein, C. J., Chan, P. H., Cadet, J. L., Carlson, E., Chen, S., Chu, L., Fahn, S., JacksonLewis, V., Kinouchi, H., Kostic, V., Kujirai, K., Mizui, A., Naini, A., Przedborski, A., and Yang, G. (1992) Resistance of SOD-transgenic mice to oxidative stress, in Gene Transfer and Therapy in the Nervous System. (Gage, F. H. and Christen Y., eds), Springer-Verlag, Berlin, pp. 106117.

    Google Scholar 

  • Fabian, R. H., DeWitt, D. S., and Kent, T. A. (1995) In vivo detection of superoxide anion production by the brain using a cytochrome C electrode. J. Cereb. Blood Flow Metab. 15, 242–247.

    Google Scholar 

  • Forsman, M., Fleischer, J. E., Milde, J. H., Stten, P. A., and Michenfelder, J. C. (1988) Superoxide dismutase and catalase failed to improve neurologic outcome after complete cerebral ischemia in the dog. Acta Anaesthesiol. Scand. 32, 152–155.

    CAS  Google Scholar 

  • Freese, A., Finklestein, S. P., and DiFiglia, M. (1992) Basic fibroblast growth factor protects striatal neurons in vitro from NMDA-receptor mediated excitotoxicity. Brain Res. 575, 351–355.

    Google Scholar 

  • Games, D., Adams, D., Alessandrini, R., Barbour, R. Berthelette, P., Blackwell, C., Can, T., Clemens, J., Donaldson, T., and Gillespie, F. (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F ß-amyloid precursor protein. Nature 373, 523–527.

    Google Scholar 

  • Ginsberg, M. C. (1990) Models of cerebral ischemia in the rodent. in Cerebral Ischemia and Resuscitation. (Schurr A., and Rigor, B. M., eds.), CRC Press, Boca Raton, FL, pp. 1–15.

    Google Scholar 

  • Gordon, J. W., Scangos, G. A., Plotkin, D. J., Barbosa, J. A., and Ruddle, F. H. (1980) Genetic transformation of mouse embryos by microinjection of purified DNA. Proc. Nat. Acad. Sci. USA 77, 7380–7384.

    Article  PubMed  CAS  Google Scholar 

  • Greenlund, L. J., Korsmeyer, S. J., and Johnson, E. M. Jr. (1995) Role of BCL-2 in the survival and function of developing and mature sympathetic neurons Neuron 15, 649–661.

    Google Scholar 

  • Hall, E. D., and Braughler, J. M. (1989) Central nervous system trauma and stroke. II. Physiological and pharmacological evidence for involvement of oxygen radicals and lipid peroxidation. Free Radic. Biol. Med. 6, 303–313.

    Google Scholar 

  • He, Y. Y., Hsu, C. Y., Ezrin, A. M., and Miller, M. S. (1993) Polyethylene glycol-conjugated super-oxide dismutase in focal cerebral ischemia-reperfusion. Am. J. Physiol. 265, H252–H256.

    Google Scholar 

  • Huang, P. L., Dawson, P. M., Bredt, D. S., Snyder, S. H., and Fishman, M. E. (1993) Targeted disruption of the neuronal nitric oxide synthase gene. Cell 75, 1273–1286.

    Article  PubMed  CAS  Google Scholar 

  • Huang, P. L., Huang, Z., Mashimo, H., Bloch, K. C., Moskowitz, M. A., Bevan, J. A., and Fishman, M. C. (1995) Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377, 239–242.

    Article  PubMed  CAS  Google Scholar 

  • Huang, T. T., Carlson, E. J., Leadon, S. A., and Epstein, C. J. (1992) Relationship of resistance to oxygen free radicals to CuZn-superoxide dismutase activity in transgenic, transfected and trisomic cells. FASEB J. 6, 903–910.

    PubMed  CAS  Google Scholar 

  • Huang, Z., Huang, P. L., Fishman, M. C., Moskowitz, M. A. (1996) Focal cerebral ischemia in mice deficient in either endothelial (eNOS) or neuronal nitric oxide (nNOS) synthase. Stroke 27, 173 (Abstract).

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Hue, R. T., and Padmaja, S. (1993) The reaction of NO with superoxide. Free Radic. Res. Commun. 18, 195–199.

    Google Scholar 

  • Hurn, S. E., Kirsch, J. R., Helfaer, M. A., Kubos, K. L., and Traystman, R. J. (1991) Polyethylene glycol-conjugated superoxide dismutase fails to augment brain superoxide dismutase activity in piglets. Stroke 22, 655–659.

    Article  Google Scholar 

  • Iadecola, C. (1993) Regulation of the cerebral microcirculation during neural activity: is nitric oxide the missing link? Trends Neurosci. 16, 206–214.

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Imaizumi, S., Woolworth, V., Fishman, R. A., and Chan, P. H. (1990) Liposomeentrapped superoxide dismutase reduces cerebral infarction in cerebral ischemia in rats. Stroke 21, 1312–1317.

    Article  PubMed  CAS  Google Scholar 

  • Inoue, T., Hirabayashi, Y., Mitsui, H., Furuta, Y., Suda, Y., Aizawa, S., and Ikawa, Y. (1994) Experimental model for MDS-like myelodysplasia in transgenic mice harboring the SV40 large-T antigen under an immunoglobulin enhancer. Leukemia 8(Suppl. 1), S202–S205.

    Google Scholar 

  • Kamii, H., Kinouchi, H., Chen, S. F., Sharp, F. R., Epstein, C. J., and Chan, P. H. (1995) SOD-1 transgenic mice: an application to the study of ischemic brain injury, in Membrane-Linked Diseases, vol. 4 (Ohnishi, S. T. ed.), CRC Press, Boca Raton, FL, pp. 423–431.

    Google Scholar 

  • Kane, D. J., Sarafian, T. A., Anton, R., Hahn, H., GraIla, E. B., Valentine, J. S., Ord, T., and Bredesen, D. (1993) Bc1–2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262, 1274–1277.

    Google Scholar 

  • Kiedrowski, L., Costa, E., and Wroblewski, J. T. (1991) Glutamate receptor agonists stimulate nitric oxide synthase in primary cultures of cerebellar granule cells. J. Neurochem. 58, 335–341.

    Article  Google Scholar 

  • Kinouchi, H., Epstein, C. J., Mizui, T., Carlson, E. J., Chen, S. F., and Chan, P. H. (1991a) Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proc. Natl. Acad. Sci. USA 88, 11158–11162.

    Article  PubMed  CAS  Google Scholar 

  • Kinouchi, H., Mizui, T., Carlson, E. J., Epstein, C. J., and Chan, P. H. (1991b) Alteration of cerebral infarction and antioxidant levels in focal cerebral ischemia in transgenic mice overexpressing CuZn-SOD. First International Neurotrauma Symposium, May 14–17,1991, Fukushima City, Japan.

    Google Scholar 

  • Kitagawa, K., Matsumoto, M., Oda, T., Niinobe, M., Hata, R., Handa, N., Fukunaga, R., Isaka, Y, Kimura, K., and Maeda, H. (1990) Free radical generation during brief periods of cerebral ischemia may trigger delayed neuronal death. Neuroscience 35, 551–558.

    Article  PubMed  CAS  Google Scholar 

  • Kondo, T., Reaume, A., Huang, T. T., Carlson, E., Chen, S., Scott, R., Epstein, C. J., and Chan, P. H. (1995) Target disruption of CuZn-superoxide dismutase gene in mice causes exacerbation of cerebral infarction and neurological deficits after focal cerebral ischemia and reperfusion. Soc. Neurosci. Abstr 12, 1268.

    Google Scholar 

  • Kontos, H. A. (1985) Oxygen radicals in cerebral vascular injury. Circ. Res. 57, 508–516.

    Article  PubMed  CAS  Google Scholar 

  • Koretsky, A. P. (1992) Investigation of cell physiology in the animal using transgenic technology. Am. J. Physiol. 262, C261–C275.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lawrence, M. S., Ho, D. Y., Sun, G. H., Steinberg, G. K., and Sapolsky, R. M. (1996) Overexpression of Bcl-2 with herpes simplex virus vectors protects CNS neurons against neurological insults in vitro and in vivo. J. Neurosci. 16, 486–496.

    PubMed  CAS  Google Scholar 

  • Leblanc, M. H., Vig, V., Randhawa, T., Smith, E. E., Parker, C. C., and Brown, E. G. (1993) Use of polyethylene glycol-bound superoxide dismutase, polyethylene glycolbound catalase, and nimodipine to prevent hypoxic ischemic injury to the brain of newborn pigs. Crit. Care Med. 21, 252–259.

    Article  PubMed  CAS  Google Scholar 

  • Lei, S. Z., Pan, Z. H., Aggarwal, S. K., Chen, H. S. V., and Lipton, S. A. (1992) Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex. Neuron 8, 1087–1099.

    Article  PubMed  CAS  Google Scholar 

  • Levanon, D., Lieman-Hurwitz, J., Dafni, N., Wigderson, M., Sherman, L., Bernstein, Y., Laver-Rudich, Z., Danciger, E., Stein, O., and Groner, Y. (1985) Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding in the Cu/Zn superoxide dismutase. EMBO J. 4, 77–84.

    Google Scholar 

  • Li, Y., Huang, T.-T., Carlson, E. J., Melov, S., Ursell, P. C., Olson, J. L., Noble, L. J., Yoshimura, M. P., Berger, C., Chan, P. H., Wallace, D. C., and Epstein, C. J. (1995) Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat. Genet. 11, 376–381.

    Google Scholar 

  • Lieman-Hurwitz, J., Dafni, N., Lavie, V., and Groner, Y. (1982) Human cytoplasmic superoxide dismutase cDNA clone: a probe for studying the molecular biology of Down syndrome. Proc. Natl. Acad. Sci. USA 79, 2808–2811.

    Article  PubMed  CAS  Google Scholar 

  • Lipton, S. A., Choi, Y. B., Pan, Z. H., Lei, S. Z., Chen, H. S., Sucher, N. J., Loscalzo, 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.

    Google Scholar 

  • Liu, T. H., Beckman, J. S., Freeman, B. A., Hogan, E. L., and Hsu, C. Y. (1989) Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury. Am. J. Physiol. 256, H589–H593.

    Google Scholar 

  • MacMicking, J. C., Nathan, C., Hom, G., Chartrain, N., Fletcher, D. S., Trubauer, M., Stevens, K., Xie, Q-W., Sokol, K., Hutchinson, N., Chen, H., and Mudgett, J. S. (1995) Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81, 641–650.

    Article  PubMed  CAS  Google Scholar 

  • MacMillan, V., Judge, D., Wiseman, A., Settle, D., Swain, J., and Davis, J. (1993) Mice expressing a bovine basic fibroblast growth factor transgene in the brain show increased resistance to hypoxemic-ischeic cerebral damage. Stroke 24, 1735–1739.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Marklund, S. L. (1982) Human copper-containing superoxide dismutase of high molecular weight. Proc. Natl. Acad. Sci. USA 79, 7634–7638.

    Article  PubMed  CAS  Google Scholar 

  • Martinou, J. C., Dubois-Dauphin, M., Staple, J. K., Rodriguez, I., Frankowski, H., Missotten, M., Albertini, P., Talabot, D., Catsicas, S., and Pietra, C. (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13, 1017–1030.

    Article  PubMed  CAS  Google Scholar 

  • Mattson, M. P., Lovell, M. A., Furukawa, K., and Markesbery, W. R. (1995) Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J. Neurochem. 65, 1740–1751.

    Google Scholar 

  • Meister, A. (1988) Glutathione metabolism and its selective modification. J. Biol. Chem. 263, 17,205–17,208.

    Google Scholar 

  • Mikawa, S., Li, Y., Huang, T. T., Carlson, E., Chen, S., Kondo, T., Murakami, K., Epstein, C. J., and Chan, P. H. (1995) Cerebral infarction is exacerbated in mitochondrial manganese superoxide dismutase (Sod-2) knockout mutant mice after focal cerebral ischemia and reperfusion. Soc. Neurosci. Abstr.. 21, 1268.

    Google Scholar 

  • Mirault, M. E., Tremblay, A., Furling, D., Trepanier, G., Dugre, F., Puymirat, J., and Pothier, F. (1994) Transgenic glutathione peroxidase mouse models for neuroprotection studies. Ann. N. Y. Acad. Sci. 738, 104–115.

    Article  PubMed  CAS  Google Scholar 

  • Mirochnitchenko, O., Palnitkar, U., Philbert, M., and Inouye, M. (1995) Thermosensitive phenotype of transgenic mice overproducing human glutathione peroxidases. Proc. Natl. Acad. Sci. USA 92, 8120–8124.

    Google Scholar 

  • Morrison, R. S., Wenzel, H. J., Kinoshita, Y., Robbins, C. A., Donehower, L. A., and Schwartzkroin, P. A. (1996) Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death. J. Neurosci. 16, 1337–1345.

    Google Scholar 

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

    Google Scholar 

  • Nagafuji, T., Matsui, T., Koide, T., and Asano, T. (1992) Blockade of nitric oxide formation by N-nitro-L-arginine mitigates ischemic brain edema and subsequent cerebral infarction in rats. Neurosci. Lett. 147, 159–162.

    Article  PubMed  CAS  Google Scholar 

  • Oberley, L. W. (1982) Superoxide Dismutase. vol. 1. CRC Press, Boca Raton, FL, pp. 1–141.

    Google Scholar 

  • Ohtsuki, T., Matsumoto, M., Kuwabara, K., Kitagawa, K., Suzuki, K., Taniguchi, N., and Kamada, T. (1992) Influence of oxidative stress on induced tolerance to ischemia in gerbil hippocampal neurons. Brain Res. 599, 246–252.

    Article  PubMed  CAS  Google Scholar 

  • Oliver, C. N., Starke-Reed, P. E., Stadtman, E. R., Liu, G. J., Carney, J. M., and Floyd, R. A. (1990) Oxidative damage to brain proteins, loss of glutamine synthetase activity and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc. Natl. Acad. Sci. USA 87, 5144–5147.

    Google Scholar 

  • Patel, M., Day, B. J., Crapo, J. C., Fridovich, I., and McNamara, J. O. (1996) Requirement for superoxide in excitotoxic cell death. Neuron 16, 345–355.

    Article  PubMed  CAS  Google Scholar 

  • Pelligrino, D. A., Koenig, H. M., and Albrecht, R. F. (1993) Nitric oxide synthesis and regional cerebral blood flow responses to hypercapnia and hypoxia in the rat. J. Cereb. Blood Flow Metab. 13, 80–87.

    Article  PubMed  CAS  Google Scholar 

  • Phelan, A. M., and Lange, D. G. (1991) Ischemia/reperfusion-induced changes in membrane fluidity characteristics of brain capillary endothelial cells and its prevention by liposomal-incorporated superoxide dismutase. Biochim. Biophys. Acta 1067, 97–102.

    Google Scholar 

  • Pigott, J. P., Donovan, D. L., Fink, J. A., and Sharp, W. V. (1988) Experimental pharmacologic cerebroprotection. J. Vasc. Surg. 7, 625–630.

    Google Scholar 

  • Popko, B., Readhead, C., Dausman, J., and Hood, L. (1990) Transgenic mice in neurobiological research, in Molecular Neurobiological Techniques (Boulton A. A., Baker G. B., and Campagnoni A. T., eds.), Humana, Clifton, NJ, pp. 221–237.

    Google Scholar 

  • Prado, R., and Watson, B. C. (1993) Effects of nitric oxide synthase inhibition on cerebral blood flow following bilateral carotid artery occlusion and recirculation in the rat. J. Cereb. Blood Flow Metab. 13, 720–723.

    Article  PubMed  CAS  Google Scholar 

  • Przedborski, S., Kostic, V., Jackson-Lewis, V., Naini, A. B., Simonetti, S., Fahn, S., Carlson, E., Epstein, C. J., and Cadet, J. L. (1992) Transgenic mice with increased Cu/ Zn-superoxide dismutase activity are resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. J. Neurosci. 12, 1658–1667.

    PubMed  CAS  Google Scholar 

  • Readhead, C., Popko, B., Takahashi, N., Shine, H. D., Saavedra, R. A., Sidman, R. L., and Hood, L. (1987) Expression of a myelin basic protein gene in transgenic Shiverer mice: correction of the dysmyelinating phenotype. Cell 48, 703–712.

    Google Scholar 

  • Rosenfeld, M. G., Crenshaw, E. B. I., and Lira, S. A. (1988) Transgenic mice: applications to the study of the nervous system. Ann. Rev. Neurosci. 11, 353–372.

    Google Scholar 

  • Schurer, L., Grogaard, B., Gerdin, B., and Arfors, K. E. (1990) Superoxide dismutase does not prevent delayed hypoperfusion after incomplete cerebral ischemia in the rat. Acta Neurochir.. 103, 163–170.

    Google Scholar 

  • Siesjö, B. K., Agardh, C. C., and Bengtsson, F. (1989) Free radicals and brain damage. Cerebrovasc. Brain Metab. Rev. 1, 165–211.

    Google Scholar 

  • Takeda, Y., Hashimoto, H., Kosaka, F., Hirakawa, M., and Inoue, M. (1993) Albuminbinding superoxide dismutase with a prolonged half-life reduces reperfusion brain injury. Am. J. Physiol. 264, H1708–H1715.

    Google Scholar 

  • Tanaka, K., Fukuuchi, Y., Gomi, S., Mihara, B., Shirai, T., Nogawa, S., Nozaki, H., and Nagata, E. (1993) Inhibition of nitric oxide synthesis impairs autoregulation of local cerebral blood flow in the rat. Neuroreport 4, 267–270.

    Google Scholar 

  • Tasdemiroglu, E., Chistenberry, P. D., Ardell, J. L., Chronister, R. B., and Taylor, A. E. (1993) Effect of superoxide dismutase on acute reperfusion injury of the rabbit brain. Acta Neurochir.. 120, 180–186.

    Google Scholar 

  • Thomas, K. R., and Capecchi, M. R. (1987) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51, 503–512.

    Article  PubMed  CAS  Google Scholar 

  • Tominaga, T., Sato, S., Ohnishi, J., and Ohnishi, S. T. (1993) Potentiation of nitric oxide formation following bilateral carotid occlusion and focal cerebral ischemia in the rat: in vivo detection of the nitric oxide radical by electron paramagnetic resonance spin trapping. Brain Res. 614, 342–346.

    Article  PubMed  CAS  Google Scholar 

  • Troy, C. M., Derossi, D., Prochiantz, A., Greene, L. A., and Shelanski, M. L. (1996) Downregulation of Cu/Zn superoxide dismutase leads to cell death via the nitric oxide-peroxynitrite pathway. J. Neurosci. 16, 253–261.

    PubMed  CAS  Google Scholar 

  • Uyama, 0., Shiratsuki, N., Matsuyama, T., Nakanishi, T., Matsumoto, Y., Yamada, T., Narita, M., and Sugita, M. (1990) Protective effects of superoxide dismutase on acute reperfusion injury of gerbil brain. Free Radic. Biol. Med. 8, 265–268.

    Google Scholar 

  • Wagner, E. F. (1990) On transferring genes into stem cells and mice. EMBO J. 9, 3025–3032.

    CAS  Google Scholar 

  • Watson, B. C., Busto, R., Goldberg, W. J., Santiso, M., Yoshida, S., and Ginsberg, M. C. (1984) Lipid peroxidation in vivo induced by reversible global ischemia in rat brain. J. Neurochem. 42, 268–274.

    Article  PubMed  CAS  Google Scholar 

  • Wei, E. P., Moskowitz, M. A., Boccalini, P., and Kontos, H. A. (1992) Calcitonin generelated peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilation in feline cerebral arterioles. Circ. Res. 70, 1313–1319.

    Article  PubMed  CAS  Google Scholar 

  • Weisbrot-Lefkowitz, M., Reuhl, K., Perry, B., Chan, P. H., Inouye, M., and Mirochnitchenko, O. (1998) Overexpression of human glutathione peroxidase protects transgenic mice against focal cerebral ischemia/reperfusion damage. Mol. Brain Res. 53, 333–338.

    Google Scholar 

  • Yang, G., Chan, P. H., Chen, J., Carlson, E., Chen, S. F., Weinstein, P., Epstein, CJ., and Kamii, H. (1994) Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia. Stroke 25, 165–170.

    Article  PubMed  Google Scholar 

  • Yang, G. Y., Chen, J., Carlson, E., Chen, S. F., Weinstein, P., Epstein, C. J., and Chan, P. H. (1993) Human Cu,Zn superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia. J. Cereb. Blood Flow Metab. 13 (Suppl. 1), S453.

    Google Scholar 

  • Yuan, J., Shaham, S., Ledoux, S., Ellis, H. M., and Horvitz, H. R. (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75, 641–652.

    Google Scholar 

  • Zhang, F. and Iadecola, C. (1993) Nitroprusside improves blood flow and reduces brain damage after focal ischemia. Neuroreport 4, 559–562.

    Article  PubMed  CAS  Google Scholar 

  • Zhong, L. T., Sarafian, T., Kane, D. J., Charles, A. C., Mah, S. P., Edwards, R. H., and Bredesen, D. E. (1993) bcl-2 inhibits death of central neural cells induced by multiple agents. Proc. Natl. Acad. Sci. USA 90, 4533–4537.

    Google Scholar 

Download references

Authors
  1. Pak H. Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

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

    Wolfgang Walz

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Chan, P.H. (1999). Oxygen Radicals. In: Walz, W. (eds) Cerebral Ischemia. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-479-5_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-479-5_5

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-4735-5

  • Online ISBN: 978-1-59259-479-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation