Gene therapy using SOD1 protects striatal neurons from experimental stroke.
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.
Davis
Alexis S
AS
Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive R200, Stanford, CA 94305-5237, United States.
Zhao
Heng
H
Sun
Guo Hua
GH
Sapolsky
Robert M
RM
Steinberg
Gary K
GK
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
C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1