Journal article
Adenovirus-Mediated Gene Transfer In Vivo to Cerebral Blood Vessels and Perivascular Tissue
Circulation research, Vol.77(1), pp.7-13
07/1995
DOI: 10.1161/01.RES.77.1.7
PMID: 7540517
Abstract
Abstract Gene transfer to blood vessels in vivo generally requires interruption of blood flow. Thus, gene transduction to cerebral blood vessels in vivo has not yet been achieved. In this study, we injected replication-deficient adenovirus into cerebrospinal fluid in an attempt to transduce genes to cerebral blood vessels. Recombinant adenovirus (1×109 infectious units) expressing nuclear-targeted bacterial β-galactosidase driven by the cytomegalovirus promoter was injected into the cisterna magna of Sprague-Dawley rats. The brains were examined histochemically after staining with 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside 1 to 7 days after injection of adenovirus. Leptomeningeal cells overlying the major arteries were efficiently transduced, and adventitial cells of large vessels and smooth muscle cells of small vessels were occasionally stained. β-Galactosidase was expressed on days 1 and 3 after injection but was undetectable by day 7. Expression of the gene was ‘targeted’ by altering the position of the head. When viral suspension was injected while the rat was in a nose-down position, the reporter gene was expressed extensively on the ventral surface of the brain, especially along the circle of Willis. When the position was changed to the nose-up or lateral position, the inferior or lateral region of the brain was stained primarily. Administration of the virus into the lateral ventricle provided extensive expression in ependymal cells and leptomeninges with some transduction to cerebral blood vessels. Thus, adenovirus injected into cerebrospinal fluid provides gene transfer in vivo to cerebral blood vessels and, with greater efficiency, to perivascular tissue. Furthermore, cisternal delivery may target specific brain regions by positioning of the head. This approach may be useful for studies of cerebral vascular biology and cerebral vascular gene therapy.
Details
- Title: Subtitle
- Adenovirus-Mediated Gene Transfer In Vivo to Cerebral Blood Vessels and Perivascular Tissue
- Creators
- Hiroaki Ooboshi - From the Departments of Internal Medicine, Physiology and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa CityMichael J Welsh - From the Departments of Internal Medicine, Physiology and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa CityC. David Rios - From the Departments of Internal Medicine, Physiology and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa CityBeverly L Davidson - From the Departments of Internal Medicine, Physiology and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa CityDonald D Heistad - From the Departments of Internal Medicine, Physiology and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.77(1), pp.7-13
- DOI
- 10.1161/01.RES.77.1.7
- PMID
- 7540517
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 07/1995
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Cardiovascular Medicine; Neuroscience and Pharmacology; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020710102771
Metrics
19 Record Views