QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (183) Citing Articles via Google Scholar Google Scholar Articles by Chan, P. H. Articles by Epstein, C. J. Search for Related Content PubMed PubMed Citation Articles by Chan, P. H. Articles by Epstein, C. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Transient Ischemic Attack

 Previous Article  |  Next Article 

The Journal of Neuroscience, October 15, 1998, 18(20):8292-8299

Overexpression of SOD1 in Transgenic Rats Protects Vulnerable Neurons Against Ischemic Damage After Global Cerebral Ischemia and Reperfusion

Pak H. Chan^{1, 3}, Makoto Kawase^{1, 3}, Kensuke Murakami¹, Sylvia F. Chen^{1, 3}, Yibing Li¹, Bernard Calagui^{1, 3}, Liza Reola^{1, 3}, Elaine Carlson², and Charles J. Epstein²

CNS Injury and Edema Research Center, Departments of ¹ Neurological Surgery and Neurology and ² Department of Pediatrics, University of California, School of Medicine, San Francisco, California 94143, and ³ Departments of Neurosurgery, Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California 94304

Transient global cerebral ischemia resulting from cardiac arrest is known to cause selective death in vulnerable neurons, including hippocampal CA₁ pyramidal neurons. It is postulated that oxygen radicals, superoxide in particular, are involved in cell death processes. To test this hypothesis, we first used in situ imaging of superoxide radical distribution by hydroethidine oxidation in vulnerable neurons. We then generated SOD1 transgenic (Tg) rats with a five-fold increase in copper zinc superoxide dismutase activity. The Tg rats and their non-Tg wild-type littermates were subjected to 10 min of global ischemia followed by 1 and 3 d of reperfusion. Neuronal damage, as assessed by cresyl violet staining and DNA fragmentation analysis, was significantly reduced in the hippocampal CA₁ region, cortex, striatum, and thalamus in SOD1 Tg rats at 3 d, as compared with the non-Tg littermates. There were no changes in the hippocampal CA₃ subregion and dentate gyrus, resistant areas in both SOD1 Tg and non-Tg rats. Quantitative analysis of the damaged CA₁ subregion showed marked neuroprotection against transient global cerebral ischemia in SOD1 Tg rats. These results suggest that superoxide radicals play a role in the delayed ischemic death of hippocampal CA₁ neurons. Our data also indicate that SOD1 Tg rats are useful tools for studying the role of oxygen radicals in the pathogenesis of neuronal death after transient global cerebral ischemia.

Key words: superoxide dismutase; transgenic rat; superoxide radicals; transient global cerebral ischemia; delayed neuronal degeneration; DNA fragmentation

---

Copyright © 1998 Society for Neuroscience  0270-6474/98/18208292-08$05.00/0

This article has been cited by other articles:

				Y. Xu, S. M. Liachenko, P. Tang, and P. H. Chan Faster Recovery of Cerebral Perfusion in SOD1-Overexpressed Rats After Cardiac Arrest and Resuscitation Stroke, July 1, 2009; 40(7): 2512 - 2518. [Abstract] [Full Text] [PDF]

				K. Niizuma, H. Endo, C. Nito, D. J. Myer, and P. H. Chan Potential Role of PUMA in Delayed Death of Hippocampal CA1 Neurons After Transient Global Cerebral Ischemia Stroke, February 1, 2009; 40(2): 618 - 625. [Abstract] [Full Text] [PDF]

				K. Niizuma, H. Endo, C. Nito, D. J. Myer, G. S. Kim, and P. H. Chan The PIDDosome mediates delayed death of hippocampal CA1 neurons after transient global cerebral ischemia in rats PNAS, October 21, 2008; 105(42): 16368 - 16373. [Abstract] [Full Text] [PDF]

				P. Cassina, A. Cassina, M. Pehar, R. Castellanos, M. Gandelman, A. de Leon, K. M. Robinson, R. P. Mason, J. S. Beckman, L. Barbeito, et al. Mitochondrial Dysfunction in SOD1G93A-Bearing Astrocytes Promotes Motor Neuron Degeneration: Prevention by Mitochondrial-Targeted Antioxidants J. Neurosci., April 16, 2008; 28(16): 4115 - 4122. [Abstract] [Full Text] [PDF]

				T. P. Obrenovitch Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia Physiol Rev, January 1, 2008; 88(1): 211 - 247. [Abstract] [Full Text] [PDF]

				D. P. D'Agostino, R. W. Putnam, and J. B. Dean Superoxide ({middle dot}O2 ) Production in CA1 Neurons of Rat Hippocampal Slices Exposed to Graded Levels of Oxygen J Neurophysiol, August 1, 2007; 98(2): 1030 - 1041. [Abstract] [Full Text] [PDF]

				X.-M. Li, J.-M. Yang, D.-H. Hu, F.-Q. Hou, M. Zhao, X.-H. Zhu, Y. Wang, J.-G. Li, P. Hu, L. Chen, et al. Contribution of Downregulation of L-type Calcium Currents to Delayed Neuronal Death in Rat Hippocampus after Global Cerebral Ischemia and Reperfusion J. Neurosci., May 9, 2007; 27(19): 5249 - 5259. [Abstract] [Full Text] [PDF]

				C. S. Lobsiger, S. Boillee, and D. W. Cleveland Inaugural Article: Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons PNAS, May 1, 2007; 104(18): 7319 - 7326. [Abstract] [Full Text] [PDF]

				H. Kamada, F. Yu, C. Nito, and P. H. Chan Influence of Hyperglycemia on Oxidative Stress and Matrix Metalloproteinase-9 Activation After Focal Cerebral Ischemia/Reperfusion in Rats: Relation to Blood-Brain Barrier Dysfunction Stroke, March 1, 2007; 38(3): 1044 - 1049. [Abstract] [Full Text] [PDF]

				H. Endo, H. Kamada, C. Nito, T. Nishi, and P. H. Chan Mitochondrial translocation of p53 mediates release of cytochrome c and hippocampal CA1 neuronal death after transient global cerebral ischemia in rats. J. Neurosci., July 26, 2006; 26(30): 7974 - 7983. [Abstract] [Full Text] [PDF]

				S. Kim-Mitsuyama, E. Yamamoto, T. Tanaka, Y. Zhan, Y. Izumi, Y. Izumiya, T. Ioroi, H. Wanibuchi, and H. Iwao Critical Role of Angiotensin II in Excess Salt-Induced Brain Oxidative Stress of Stroke-Prone Spontaneously Hypertensive Rats Stroke, May 1, 2005; 36(5): 1077 - 1082. [Abstract] [Full Text] [PDF]

				P. H. Chan Future Targets and Cascades for Neuroprotective Strategies Stroke, November 1, 2004; 35(11_suppl_1): 2748 - 2750. [Abstract] [Full Text] [PDF]

				S. Okuno, A. Saito, T. Hayashi, and P. H. Chan The c-Jun N-Terminal Protein Kinase Signaling Pathway Mediates Bax Activation and Subsequent Neuronal Apoptosis through Interaction with Bim after Transient Focal Cerebral Ischemia J. Neurosci., September 8, 2004; 24(36): 7879 - 7887. [Abstract] [Full Text] [PDF]

				A. I. Rojo, M. Salinas, D. Martin, R. Perona, and A. Cuadrado Regulation of Cu/Zn-Superoxide Dismutase Expression via the Phosphatidylinositol 3 Kinase/Akt Pathway and Nuclear Factor-{kappa}B J. Neurosci., August 18, 2004; 24(33): 7324 - 7334. [Abstract] [Full Text] [PDF]

				F. M. Faraci and S. P. Didion Vascular Protection: Superoxide Dismutase Isoforms in the Vessel Wall Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1367 - 1373. [Abstract] [Full Text] [PDF]

				S.-R. Lee, K. Tsuji, S.-R. Lee, and E. H. Lo Role of Matrix Metalloproteinases in Delayed Neuronal Damage after Transient Global Cerebral Ischemia J. Neurosci., January 21, 2004; 24(3): 671 - 678. [Abstract] [Full Text] [PDF]

				G. W. Kim, Y. Gasche, S. Grzeschik, J.-C. Copin, C. M. Maier, and P. H. Chan Neurodegeneration in Striatum Induced by the Mitochondrial Toxin 3-Nitropropionic Acid: Role of Matrix Metalloproteinase-9 in Early Blood-Brain Barrier Disruption? J. Neurosci., September 24, 2003; 23(25): 8733 - 8742. [Abstract] [Full Text] [PDF]

				N. Noshita, T. Sugawara, A. Lewen, T. Hayashi, and P. H. Chan Copper-Zinc Superoxide Dismutase Affects Akt Activation After Transient Focal Cerebral Ischemia in Mice Stroke, June 1, 2003; 34(6): 1513 - 1518. [Abstract] [Full Text] [PDF]

				S. Paruthiyil, M. E. Majdoubi, M. Conti, and R. I. Weiner Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats PNAS, December 24, 2002; 99(26): 17191 - 17196. [Abstract] [Full Text] [PDF]

				N. Noshita, T. Sugawara, T. Hayashi, A. Lewen, G. Omar, and P. H. Chan Copper/Zinc Superoxide Dismutase Attenuates Neuronal Cell Death by Preventing Extracellular Signal-Regulated Kinase Activation after Transient Focal Cerebral Ischemia in Mice J. Neurosci., September 15, 2002; 22(18): 7923 - 7930. [Abstract] [Full Text] [PDF]

				C. M. Maier and P. H. Chan Book Review: Role of Superoxide Dismutases in Oxidative Damage and Neurodegenerative Disorders Neuroscientist, August 1, 2002; 8(4): 323 - 334. [Abstract] [PDF]

				G. W. Kim, T. Kondo, N. Noshita, and P. H. Chan Manganese Superoxide Dismutase Deficiency Exacerbates Cerebral Infarction After Focal Cerebral Ischemia/Reperfusion in Mice: Implications for the Production and Role of Superoxide Radicals Stroke, March 1, 2002; 33(3): 809 - 815. [Abstract] [Full Text] [PDF]

				T. Sugawara, N. Noshita, A. Lewen, Y. Gasche, M. Ferrand-Drake, M. Fujimura, Y. Morita-Fujimura, and P. H. Chan Overexpression of Copper/Zinc Superoxide Dismutase in Transgenic Rats Protects Vulnerable Neurons against Ischemic Damage by Blocking the Mitochondrial Pathway of Caspase Activation J. Neurosci., January 1, 2002; 22(1): 209 - 217. [Abstract] [Full Text] [PDF]

				Y. Morita-Fujimura, M. Fujimura, T. Yoshimoto, and P. H. Chan Superoxide During Reperfusion Contributes to Caspase-8 Expression and Apoptosis After Transient Focal Stroke Stroke, October 1, 2001; 32(10): 2356 - 2361. [Abstract] [Full Text] [PDF]

				R. M. Adibhatla, J.F. Hatcher, and R.J. Dempsey Effects of Citicoline on Phospholipid and Glutathione Levels in Transient Cerebral Ischemia Stroke, October 1, 2001; 32(10): 2376 - 2381. [Abstract] [Full Text] [PDF]

				T. Sugawara, N. Noshita, A. Lewen, G. W. Kim, and P. H. Chan Neuronal Expression of the DNA Repair Protein Ku 70 After Ischemic Preconditioning Corresponds to Tolerance to Global Cerebral Ischemia Stroke, October 1, 2001; 32(10): 2388 - 2393. [Abstract] [Full Text] [PDF]

				C.-Y. Huang, M. Fujimura, Y.-Y. Chang, and P. H. Chan Overexpression of Copper-Zinc Superoxide Dismutase Attenuates Acute Activation of Activator Protein-1 After Transient Focal Cerebral Ischemia in Mice Stroke, March 1, 2001; 32(3): 741 - 747. [Abstract] [Full Text] [PDF]

				K. Sampei, A. S. Mandir, Y. Asano, P. C. Wong, R. J. Traystman, V. L. Dawson, T. M. Dawson, P. D. Hurn, and C. Y. Hsu Stroke Outcome in Double-Mutant Antioxidant Transgenic Mice Editorial Comment Stroke, November 1, 2000; 31(11): 2685 - 2691. [Abstract] [Full Text] [PDF]

				N. Derugin, M. Wendland, K. Muramatsu, T. P. L. Roberts, G. Gregory, D. M. Ferriero, Z. S. Vexler, and W. D. Dietrich Evolution of Brain Injury After Transient Middle Cerebral Artery Occlusion in Neonatal Rats Editorial Comment Stroke, July 1, 2000; 31(7): 1752 - 1761. [Abstract] [Full Text] [PDF]

				M. Fujimura, Y. Morita-Fujimura, N. Noshita, T. Sugawara, M. Kawase, and P. H. Chan The Cytosolic Antioxidant Copper/Zinc-Superoxide Dismutase Prevents the Early Release of Mitochondrial Cytochrome c in Ischemic Brain after Transient Focal Cerebral Ischemia in Mice J. Neurosci., April 15, 2000; 20(8): 2817 - 2824. [Abstract] [Full Text] [PDF]

				M. Fujimura, Y. Morita-Fujimura, P. Narasimhan, J.-C. Copin, M. Kawase, P. H. Chan, and C. Y. Hsu Copper-Zinc Superoxide Dismutase Prevents the Early Decrease of Apurinic/Apyrimidinic Endonuclease and Subsequent DNA Fragmentation After Transient Focal Cerebral Ischemia in Mice • Editorial Comment Stroke, November 1, 1999; 30(11): 2408 - 2415. [Abstract] [Full Text] [PDF]

				P. Lipton Ischemic Cell Death in Brain Neurons Physiol Rev, October 1, 1999; 79(4): 1431 - 1568. [Abstract] [Full Text] [PDF]

				M. Kawase, K. Murakami, M. Fujimura, Y. Morita-Fujimura, Y. Gasche, T. Kondo, R. W. Scott, P. H. Chan, and M. S. Wolin Exacerbation of Delayed Cell Injury After Transient Global Ischemia in Mutant Mice With CuZn Superoxide Dismutase Deficiency • Editorial Comment Stroke, September 1, 1999; 30(9): 1962 - 1968. [Abstract] [Full Text] [PDF]

				H. Sheng, D. T. Laskowitz, G. B. Mackensen, M. Kudo, R. D. Pearlstein, D. S. Warner, and C. Iadecola Apolipoprotein E Deficiency Worsens Outcome From Global Cerebral Ischemia in the Mouse • Editorial Comment Stroke, May 1, 1999; 30(5): 1118 - 1124. [Abstract] [Full Text] [PDF]

				M. Kawase, M. Fujimura, Y. Morita-Fujimura, P. H. Chan, and C. Iadecola Reduction of Apurinic/Apyrimidinic Endonuclease Expression After Transient Global Cerebral Ischemia in Rats : Implication of the Failure of DNA Repair in Neuronal Apoptosis • Editorial Comment: Implication of the Failure of DNA Repair in Neuronal Apoptosis Stroke, February 1, 1999; 30(2): 441 - 449. [Abstract] [Full Text] [PDF]

				K. Kitagawa, M. Matsumoto, Y. Tsujimoto, T. Ohtsuki, K. Kuwabara, K. Matsushita, G. Yang, H. Tanabe, J.-C. Martinou, M. Hori, et al. Amelioration of Hippocampal Neuronal Damage After Global Ischemia by Neuronal Overexpression of BCL-2 in Transgenic Mice • Editorial Comment Stroke, December 1, 1998; 29(12): 2616 - 2621. [Abstract] [Full Text] [PDF]

				T. Sugawara, M. Fujimura, Y. Morita-Fujimura, M. Kawase, and P. H. Chan Mitochondrial Release of Cytochrome c Corresponds to the Selective Vulnerability of Hippocampal CA1 Neurons in Rats after Transient Global Cerebral Ischemia J. Neurosci., November 15, 1999; 19(22): RC39 - RC39. [Abstract] [Full Text] [PDF]

				K.-M. Noh and J.-Y. Koh Induction and Activation by Zinc of NADPH Oxidase in Cultured Cortical Neurons and Astrocytes J. Neurosci., December 1, 2000; 20(23): RC111 - RC111. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help