Journal article
Gene Transfer to Cerebral Blood Vessels After Subarachnoid Hemorrhage
Stroke (1970), Vol.28(4), pp.822-829
04/1997
DOI: 10.1161/01.STR.28.4.822
PMID: 9099203
Abstract
Background and Purpose Vasospasm remains a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage. One step toward gene therapy to prevent spasm of cerebral vessels is to determine whether subarachnoid blood prevents transgene expression.
Methods Vasospasm was induced in mongrel dogs using the double-hemorrhage intracranial-injection model. Diameter of the basilar artery was assessed by angiography, and profound vasospasm (>50% decrease in diameter) was demonstrated at 4 and 7 days. Recombinant adenovirus expressing nuclear-targeted β-galactosidase (reporter gene) under the control of the cytomegalovirus promoter was injected into the cisterna magna at the same time as (n=9) or 2 days after (n=4) injection of blood for induction of vasospasm. Brains were removed and examined histochemically for expression of nuclear β-galactosidase.
Results At 2 to 7 days, β-galactosidase was expressed in leptomeninges over the brain stem, cortex, cerebral arteries, in small vessels in the cerebrum and brain stem, and in the ependymal lining of the ventricles. Transgene expression was observed in adventitia of blood vessels but not in vascular muscle or endothelium. Transgene expression was observed after simultaneous injection of virus and blood or when virus was injected 2 days after blood.
Conclusions The findings indicate that intracisternal injection of recombinant adenovirus can be used for gene transfer to cerebral blood vessels and overlying meninges, even in the presence of cisternal blood. We speculate that transfer of genes using recombinant viral vectors that encode for enzymes with vasodilator function to cerebral blood vessels and perivascular tissues may be useful for prevention or treatment of cerebral vasospasm after subarachnoid hemorrhage.
Details
- Title: Subtitle
- Gene Transfer to Cerebral Blood Vessels After Subarachnoid Hemorrhage
- Creators
- Michael G Muhonen - From the Departments of Surgery (Division of Neurosurgery), Internal Medicine, and Pharmacology, University of Iowa College of Medicine; the Howard Hughes Medical Institute (M.J.W.); and the Veterans Administration Medical Center, Iowa City, IowaHiroaki Ooboshi - From the Departments of Surgery (Division of Neurosurgery), Internal Medicine, and Pharmacology, University of Iowa College of Medicine; the Howard Hughes Medical Institute (M.J.W.); and the Veterans Administration Medical Center, Iowa City, IowaMichael J Welsh - From the Departments of Surgery (Division of Neurosurgery), Internal Medicine, and Pharmacology, University of Iowa College of Medicine; the Howard Hughes Medical Institute (M.J.W.); and the Veterans Administration Medical Center, Iowa City, IowaBeverly L Davidson - From the Departments of Surgery (Division of Neurosurgery), Internal Medicine, and Pharmacology, University of Iowa College of Medicine; the Howard Hughes Medical Institute (M.J.W.); and the Veterans Administration Medical Center, Iowa City, IowaDonald D Heistad - From the Departments of Surgery (Division of Neurosurgery), Internal Medicine, and Pharmacology, University of Iowa College of Medicine; the Howard Hughes Medical Institute (M.J.W.); and the Veterans Administration Medical Center, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.28(4), pp.822-829
- DOI
- 10.1161/01.STR.28.4.822
- PMID
- 9099203
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Language
- English
- Date published
- 04/1997
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Cardiovascular Medicine; Neuroscience and Pharmacology; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020741202771
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