This Article Full Text Full Text (PDF) All Versions of this Article: 34/2/434    most recent 01.STR.0000051586.96022.37v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Watanabe, Y. Articles by Heistad, D. D. Search for Related Content PubMed PubMed Citation Articles by Watanabe, Y. Articles by Heistad, D. D. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Genes and Gene Therapy Related Collections Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage Gene therapy Oxidant stress Other Vascular biology

(Stroke. 2003;34:434.)
© 2003 American Heart Association, Inc.

Original Contributions

Gene Transfer of Extracellular Superoxide Dismutase Reduces Cerebral Vasospasm After Subarachnoid Hemorrhage

Yoshimasa Watanabe, MD; Yi Chu, PhD; Jon J. Andresen, BA; Hiroshi Nakane, MD; Frank M. Faraci, PhD Donald D. Heistad, MD

From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa.

Correspondence to Donald D. Heistad, MD, Department of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Dr, Iowa City, IA 52242. E-mail donald-heistad{at}uiowa.edu

Background and Purpose— Superoxide may play an important role in cerebral vasospasm after subarachnoid hemorrhage (SAH). Our first goal was to determine the effect of gene transfer of extracellular superoxide dismutase (ECSOD) on vasospasm after experimental SAH. Our second goal was to determine whether tissue binding of ECSOD via the heparin-binding domain (HBD) is important for the effect of the enzyme. Thus, we examined effects of gene transfer of ECSOD with the HBD deleted (ECSODHBD).

Methods— Adenovirus expressing human ECSOD (AdECSOD), ECSODHBD (AdECSODHBD), or no transgene (AdBglII) was injected into the cisterna magna of anesthetized rabbits 30 minutes after induction of experimental SAH. Cerebral angiography, an assay for ECSOD activity in cerebrospinal fluid (CSF), and Western blotting for human ECSOD in the basilar artery were performed.

Results— Baseline diameter of the basilar artery averaged 0.77±0.01 mm (mean±SEM) and was similar in all treatment groups. Decreases in diameter of the basilar artery 2 days after SAH were smaller after AdECSOD (11±3%; n=10) than after AdBglII (25±4%; n=7; P<0.05). ECSOD activity was not detected in CSF before SAH and gene transfer. Of 8 rabbits treated with AdECSOD, in which ECSOD activity in CSF was measured after SAH, 5 animals had detectable ECSOD activity in CSF (46±13 U/mL). In these 5 rabbits, the diameter decreased by only 6±3%, and ECSOD protein was detected in the basilar artery. After AdECSODHBD (n=4), despite high levels of ECSOD activity in CSF (91±19 U/mL), vessel diameter decreased by 20±2%, and no ECSODHBD protein was detected in the basilar artery.

Conclusions— Gene transfer of ECSOD reduces cerebral vasospasm after experimental SAH. Tissue binding of the enzyme is essential for cerebral vascular effects of ECSOD.

Key Words: gene transfer • subarachnoid hemorrhage • superoxide dismutase • vasospasm, intracranial • rabbits

This article has been cited by other articles:

				M. Kerkeni, F. Added, M. B. Farhat, A. Miled, F. Trivin, and K. Maaroufi Hyperhomocysteinaemia and parameters of antioxidative defence in Tunisian patients with coronary heart disease Ann Clin Biochem, March 1, 2008; 45(2): 193 - 198. [Abstract] [Full Text] [PDF]

				R. O. Hopkins, L. K. Weaver, K. J. Valentine, C. Mower, S. Churchill, and J. Carlquist Apolipoprotein E Genotype and Response of Carbon Monoxide Poisoning to Hyperbaric Oxygen Treatment Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 1001 - 1006. [Abstract] [Full Text] [PDF]

				D. D. Lund, Y. Chu, R. M. Brooks, F. M. Faraci, and D. D. Heistad Effects of a common human gene variant of extracellular superoxide dismutase on endothelial function after endotoxin in mice J. Physiol., October 15, 2007; 584(2): 583 - 590. [Abstract] [Full Text] [PDF]

				T. Ogawa, S. Ono, T. Ichikawa, S. Arimitsu, K. Onoda, K. Tokunaga, K. Sugiu, K. Tomizawa, H. Matsui, and I. Date Novel Protein Transduction Method by Using 11R: An Effective New Drug Delivery System for the Treatment of Cerebrovascular Diseases Stroke, April 1, 2007; 38(4): 1354 - 1361. [Abstract] [Full Text] [PDF]

				O. Jung, S. L. Marklund, N. Xia, R. Busse, and R. P. Brandes Inactivation of Extracellular Superoxide Dismutase Contributes to the Development of High-Volume Hypertension Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 470 - 477. [Abstract] [Full Text] [PDF]

				J. Kitayama, C. Yi, F. M. Faraci, and D. D. Heistad Modulation of Dilator Responses of Cerebral Arterioles by Extracellular Superoxide Dismutase Stroke, November 1, 2006; 37(11): 2802 - 2806. [Abstract] [Full Text] [PDF]

				Y. Chu, R. Piper, S. Richardson, Y. Watanabe, P. Patel, and D. D. Heistad Endocytosis of Extracellular Superoxide Dismutase Into Endothelial Cells: Role of the Heparin-Binding Domain Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 1985 - 1990. [Abstract] [Full Text] [PDF]

				F. M. Faraci Reactive oxygen species: influence on cerebral vascular tone J Appl Physiol, February 1, 2006; 100(2): 739 - 743. [Abstract] [Full Text] [PDF]

				Y. Chu, A. Alwahdani, S. Iida, D. D. Lund, F. M. Faraci, and D. D. Heistad Vascular Effects of the Human Extracellular Superoxide Dismutase R213G Variant Circulation, August 16, 2005; 112(7): 1047 - 1053. [Abstract] [Full Text] [PDF]

				S. Iida, Y. Chu, J. Francis, R. M. Weiss, C. A. Gunnett, F. M. Faraci, and D. D. Heistad Gene transfer of extracellular superoxide dismutase improves endothelial function in rats with heart failure Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H525 - H532. [Abstract] [Full Text] [PDF]

				Y. Watanabe, F. M. Faraci, and D. D. Heistad Activation of Rho-associated kinase during augmented contraction of the basilar artery to serotonin after subarachnoid hemorrhage Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2653 - H2658. [Abstract] [Full Text] [PDF]

				Y. Watanabe and D. D. Heistad Targeting cerebral arteries for gene therapy Exp Physiol, May 1, 2005; 90(3): 327 - 331. [Abstract] [Full Text] [PDF]

				L. A. Lanterna, M. Rigoldi, G. Tredici, F. Biroli, C. Cesana, S. M. Gaini, and L. Dalpra APOE influences vasospasm and cognition of noncomatose patients with subarachnoid hemorrhage Neurology, April 12, 2005; 64(7): 1238 - 1244. [Abstract] [Full Text] [PDF]

				M. Yamaguchi, C. Zhou, D. D. Heistad, Y. Watanabe, and J. H. Zhang Gene Transfer of Extracellular Superoxide Dismutase Failed to Prevent Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage Stroke, November 1, 2004; 35(11): 2512 - 2517. [Abstract] [Full Text] [PDF]

				D. D. Lund, C. A. Gunnett, Y. Chu, R. M. Brooks, F. M. Faraci, and D. D. Heistad Gene transfer of extracellular superoxide dismutase improves relaxation of aorta after treatment with endotoxin Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H805 - H811. [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]

				F. M. Faraci Vascular Protection Stroke, February 1, 2003; 34(2): 327 - 329. [Full Text] [PDF]