title: Transplantation of neural stem cells that overexpress SOD1 enhances amelioration of intracerebral hemorrhage in mice.
abstract: Previous studies have shown that intraparenchymal transplantation of neural stem cells (NSCs) ameliorates neurologic deficits in animals with intracerebral hemorrhage (ICH). However, massive grafted cell death after transplantation, possibly caused by a hostile host brain environment, lessens the effectiveness of this approach. We focused on the effect of oxidative stress against grafted NSCs and hypothesized that conferring antioxidant properties to transplanted NSCs may overcome their death and enhance neuroprotection after ICH. Copper/zinc-superoxide dismutase (SOD1) is a specific antioxidant enzyme that counteracts superoxide anions. We investigated whether genetic manipulation to overexpress SOD1 enhances survival of grafted NSCs and accelerates amelioration of ICH. Neural stem cells that overexpress SOD1 were administered intracerebrally 3 days after ICH in a mouse model. Histologic and behavioral tests were examined after ICH. Copper/zinc-superoxide dismutase overexpression protected the grafted NSCs via a decrease in production of reactive oxygen species. This resulted in an increase in paracrine factors released by the NSCs, and an increase in surviving neurons in the striatum and a reduction in striatal atrophy. In addition, SOD1 overexpression showed progressive improvement in behavioral recovery. Our results suggest that enhanced antioxidative activity in NSCs improves efficacy of stem cell therapy for ICH.
authors: 1] Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA [2] Department of Neurology and Neurological Sciences and Program in Neurosciences, Stanford University School of Medicine, Stanford, California, USA.
authors: Takuma
authors: T
authors: Wakai
authors: 1] Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA [2] Department of Neurology and Neurological Sciences and Program in Neurosciences, Stanford University School of Medicine, Stanford, California, USA.
authors: Hiroyuki
authors: H
authors: Sakata
authors: 1] Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA [2] Department of Neurology and Neurological Sciences and Program in Neurosciences, Stanford University School of Medicine, Stanford, California, USA.
authors: Purnima
authors: P
authors: Narasimhan
authors: Department of Neurosurgery, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors: Hideyuki
authors: H
authors: Yoshioka
authors: Department of Neurosurgery, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors: Hiroyuki
authors: H
authors: Kinouchi
authors: 1] Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA [2] Department of Neurology and Neurological Sciences and Program in Neurosciences, Stanford University School of Medicine, Stanford, California, USA.
authors: Pak H
authors: PH
authors: Chan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D002469:Cell Separation; D002470:Cell Survival / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000503:physiopathology / Q000628:therapy*; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000201:enzymology / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000379:methods; D013482:Superoxide Dismutase / Q000235:genetics* / Q000502:physiology; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D049452:Green Fluorescent Proteins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1