Gene transfer of extracellular superoxide dismutase failed to prevent cerebral vasospasm after experimental subarachnoid hemorrhage

Mitsuo YAMAGUCHI; Changman Zhou; Donald D HEISTAD; Yoshimasa WATANABE; John H ZHANG

doi:10.1161/01.STR.0000145198.07723.8e

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Gene transfer of extracellular superoxide dismutase failed to prevent cerebral vasospasm after experimental subarachnoid hemorrhage

Journal article

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Gene transfer of extracellular superoxide dismutase failed to prevent cerebral vasospasm after experimental subarachnoid hemorrhage

Mitsuo YAMAGUCHI, Changman Zhou, Donald D HEISTAD, Yoshimasa WATANABE and John H ZHANG

Stroke (1970), Vol.35(11), pp.2512-2517

2004

DOI: 10.1161/01.STR.0000145198.07723.8e

PMID: 15472087

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Abstract

Background and Purpose— We examined the therapeutic effect of human extracellular superoxide dismutase (ECSOD) gene transfer in the prevention of delayed cerebral vasospasm after experimental subarachnoid hemorrhage (SAH) because it was reported ECSOD relieved early-stage vasospasm. Methods— Twenty mongrel dogs were divided randomly into 4 groups to serve as control, SAH, SAH+adenovirus ECSOD (AdECSOD), and SAH+no transgene (AdBglII) groups, respectively. An established canine double-hemorrhage model of SAH was used by injecting autologous arterial blood into the cisterna magna on day 0 and day 2. Angiography was performed at day 0 and day 7. Clinical behavior, cerebrospinal fluid (CSF) ECSOD activity, CSF leukocyte count, morphology, and human ECSOD expression (RT-PCR) in the basilar arteries were evaluated. Results— Severe vasospasm was obtained in SAH, SAH+AdECSOD, and SAH+AdBglII gene–transferred dogs, and the residual diameters of the basilar artery were 41±1%, 39±4%, and 49±4%, respectively. Increased CSF activity of ECSOD was obtained in SAH+AdECSOD (162±23 U/mL) when compared with SAH (26±2) and SAH+AdBglII (25±3) dogs. RT-PCR confirmed successful gene transfer in the basilar arteries from SAH+AdECSOD dogs. Increased leukocyte counts were observed in the CSF and in the subarachnoid space, especially in SAH+AdECSOD and SAH+AdBglII dogs. Conclusions— Gene transfer of human ECSOD failed to prevent delayed cerebral vasospasm.

Biotechnology

Neurology

Toxicology

Gene Therapy

Fundamental and applied biological sciences. Psychology

Drug addictions

Health. Pharmaceutical industry

Industrial applications and implications. Economical aspects

Biological and medical sciences

Vascular diseases and vascular malformations of the nervous system

Medical sciences

Details

Title: Subtitle: Gene transfer of extracellular superoxide dismutase failed to prevent cerebral vasospasm after experimental subarachnoid hemorrhage
Creators: Mitsuo YAMAGUCHI - Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, La, United States
Changman Zhou - Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, La, United States
Donald D HEISTAD - Department of Internal Medicine, University of Iowa, Iowa City, United States
Yoshimasa WATANABE - Department of Internal Medicine, University of Iowa, Iowa City, United States
John H ZHANG - Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, La, United States
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.35(11), pp.2512-2517
Publisher: Lippincott Williams & Wilkins; Hagerstown, MD
DOI: 10.1161/01.STR.0000145198.07723.8e
PMID: 15472087
ISSN: 0039-2499
eISSN: 1524-4628
Language: English
Date published: 2004
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040588602771

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