title: Attenuation of stroke size in rats using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist in brain.
abstract: Adenoviruses have been proposed as potential vectors for gene therapy in the central nervous system, but there are no reports of their use in the treatment of a brain disease. Because central administration of interleukin-1 receptor antagonist protein (IL-1ra) reduces ischemic brain damage, we determined whether a recombinant adenovirus vector carrying the human IL-1ra cDNA (Ad.RSVIL-1ra) could be used to ameliorate brain injury in permanent focal ischemia. Groups of six rats received intraventricular injections of Ad.RSVIL-1ra or a control adenovirus containing the Escherichia coli beta-galactosidase gene (Ad.RSVlacZ). Histochemical staining for beta-galactosidase 5 days after virus injection indicated that transgene expression was confined primarily to the cells lining the ventricle. The concentrations of IL-1ra injected animals, achieving levels of 9.1 +/- 3.3 ng/g in brain and 23.7 +/- 22.5 ng/ml in CSF. In these animals, cerebral infarct volume resulting from 24 h of permanent middle cerebral artery occlusion was reduced 64%. These studies demonstrate that adenoviral vectors can be used to deliver genes that attenuate brain injury.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor 48109-0532, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Betz
authors.forename: G Y
authors.initials: GY
authors.lastname: Yang
authors.forename: B L
authors.initials: BL
authors.lastname: Davidson
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002561:Cerebrovascular Disorders / Q000628:therapy*; D004926:Escherichia coli / Q000201:enzymology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000235:genetics*; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D001616:beta-Galactosidase