title: Gene therapy using SOD1 protects striatal neurons from experimental stroke.
abstract: Reactive oxygen species contribute to neuronal death following cerebral ischemia. Prior studies using transgenic animals have demonstrated the neuroprotective effect of the antioxidant, copper/zinc superoxide dismutase (SOD1). In this study, we investigated whether SOD1 overexpression using gene therapy techniques in non-transgenic animals would increase neuronal survival. A neurotropic, herpes simplex virus-1 (HSV-1) vector containing the SOD1 gene was injected into the striatum either before or after transient focal cerebral ischemia. Striatal neuron survival at 2 days was improved by 52% when vector was delivered 12-15 h prior to ischemia and by 53% when vector delivery was delayed 2 h following ischemia. These data add to the growing literature, which suggests that an antioxidant approach, perhaps by employing gene therapy techniques, may be beneficial in the treatment of stroke.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive R200, Stanford, CA 94305-5237, United States.
authors.forename: Alexis S
authors.initials: AS
authors.lastname: Davis
authors.forename: Heng
authors.initials: H
authors.lastname: Zhao
authors.forename: Guo Hua
authors.initials: GH
authors.lastname: Sun
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sapolsky
authors.forename: Gary K
authors.initials: GK
authors.lastname: Steinberg
mesh_terms: D000818:Animals; D002470:Cell Survival; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D018259:Herpesvirus 1, Human / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000235:genetics / Q000473:pathology / Q000628:therapy; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D000072105:Superoxide Dismutase-1; D014162:Transfection
chemical_list: C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1