Abstract
1. Nitric oxide radicals (NO) play an important role in the pathophysiology of focal cerebral ischemia.
2. Vascular NO can reduce ischemic brain injury by increasing CBF, whereas neuronal NO may mediate neurotoxicity following brain ischemia, mainly by its reaction with superoxide to generate peroxynitrite.
3. These findings could contribute to a strategy for the treatment of cerebral ischemia.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Babbedge, R. C., Bland-Ward, P. A., Hart, S. L., and Moore, P. K. (1993). Inhibition of rat cerebellar nitric oxide synthase by 7-nitro indazole and related substituted indazoles. Br. J. Pharmacol. 110:225–228.
Beckman, J. S., Beckman T. W., Chen, J., Marshall, P. A., and Freeman B. A. (1990). Apparent hydroxyl radical production by peroxynitrite: Implication for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. USA 87:1620–1624.
Beckman, J. S., Carson, M., Smith, C. D., and Koppenol, W. H. (1993). ALS, SOD, and peroxynitrite. Nature 364:584.
Chan, P. H. (1988). The role of oxygen radicals in brain injury and edema. In Chow, C. K. (ed.), Cellular Antioxidant Defense Mechanisms, CRC Press, Boca Raton, FL, pp. 89–109.
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 CuZn-superoxide dismutase. Ann. Neurol. 29:482–486.
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 Bazan, N. G., Braquet, P., and Ginsberg, M. (eds.), Neurochemical Correlates of Cerebral Ischemia, Plenum Press, New York, pp. 277–294.
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. In Kogure, K., and Siesjo, B. K. (eds.), Molecular Mechanisms of Ischemic Brain Damage, Elsevier, Amsterdam, pp. 97–104.
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.
Chen, S. T., Hsu, C. Y., Hogan, E. L., Marica, H., and Balentine, J. D. (1986). A model focal ischemic stroke in the rat: Reproducible extensive cortical infarction. Stroke 17:738–743.
Choi, D. W. (1993). Nitric oxide: Foe or friend to the injured brain? Proc. Natl. Acad. Sci. USA 90:9741–9743.
Dawson, T. M., Bredt, D. S., Fotuki, M., Hwang, P. M., and Snyder, S. H. (1991). Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc. Natl. Acad. Sci. USA 88:7797–7801.
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. 32:2651–2661.
Dawson, V. L., Dawson, T. M. Bartely, D. A., Uhl, G. R., and Snyder, S. H. (1993). Mechanism of nitric oxide-mediated neurotoxicity in primary brain cultures. J. Neurosci. 13:2651–2661.
Epstein, C. J., Avraham, K. B., Lovett, M., Smith, S., Elroy-Sein, O., Rotman, G., Bry, C., and Groner, Y. (1987). Transgenic mice wit increased Cu/Zn-superoxide dismutase activity: Animal model of dosage effects in Down syndrome. Proc. Natl. Acad. Sci. USA 84:8044–8048.
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.
Hue, R. T., and Padmaja, S. (1993). The reaction of NO with superoxide. Free Radic. Res. Commun. 18:195–199.
Iadecola, C. A., Moskowitz, M. A., and Lassen, N. A. (1994). State of the art review: Nitric oxide synthase inhibition and cerebrovascular regulation. J. Cereb. Blood Flow and Metab. 14:175–192.
Imaizumi, S., Woolworth, V., Fishman, R. A., and Chan, P. H. (1990). Liposome-entrapped superoxide dismutase reduces cerebral infarction in cerebral ischemia in rats. Stroke 21:1312–1317.
Kamii, H., Kinouchi, H., Sharp, F. R., Koistinaho, J., Epstein, C. J., and Chan, P. H. (1994). Prolonged expression of hsp70 mRNA following transient focal cerebral ischemia in transgenic mice overexpressing CuZn-superoxide dismutase. J. Cereb. Blood Flow Metab. 14:478–486.
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.
Kinouchi, H., Epstein, C. J., Mizui, T., Carlson, E., Chen, S. F., and Chan, P. H. (1991). Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proc. Natl. Acad. Sci. USA 88:11158–11162.
Kontos, H. A. (1985). Oxygen radicals in cerebral vascular injury. Circ. Res. 57:508–516.
Lei, S., 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.
Liu, T. H., Beckman, J. S., Freeman, B. A., Hogan, E. L., and Hsu, C. Y. (1989). Polyethylene glycolconjugated superoxide dismutase and catalase reduce ischemic brain injury. Am. J. Physiol. 256:H589–H593.
Moncada, S., Palmer, R. M., and Higgs, E. A. (1991). Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43:109–142.
Nagafuji, T., Matsui, T., Koide, T., and Asano, T. (1992). Blockade of nitric oxide formation by N-nitric-L-arginine mitigates ischemic brain edema and subsequent cerebral infarction in rats. Neurosci. Lett. 147:159–162.
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.
Prado, R., and Watson, B. D. (1993). Effects of nitric oxide synthase inhibition on cerebral blood fowl following bilateral carotid artery occlusion and recirculation in the rat. J. Cereb. Blood Flow Metab. 13:720–723.
Siesjo, B. K., Ahardh, C. D., and Bengtsson, F. (1989). Free radicals and brain damage. Cereb. Brain Metab. Rev. 6:303–313.
Tanaka, K., Fukuuchi, Y., Gomi, S., Mihara, B., Shirai, T., Nogawa, S., Hozuki, H., and Nagata, E. (1993). Inhibition of nitric oxide synthesis impairs autoregulation of local cerebral blood flow in the rat. Neuroreport 4:267–270.
Wei, E. P., Moskowitz, M. A., Boccalini, P., and Kontos, H. A. (1992). Calcitonin gene related peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilation in feline cerebral arterioles. Circ. Res. 70:1313–1319.
Zhang, F., and Iadecola, C. (1993). Nitroprusside improves blood flow and reduces brain damage after focal ischemia. Neuroreport 4:559–562.
Xue, D., Slivka, A., and Buchan, A. M. (1992). Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats. Stroke 23:894–899.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kinouchi, H., Kamii, H., Mikawa, S. et al. Role of Superoxide Dismutase in Ischemic Brain Injury: A Study Using SOD-1 Transgenic Mice. Cell Mol Neurobiol 18, 609–620 (1998). https://doi.org/10.1023/A:1020677701368
Issue Date:
DOI: https://doi.org/10.1023/A:1020677701368