共 34 条
Neural Stem Cells Genetically Modified to Overexpress Cu/Zn-Superoxide Dismutase Enhance Amelioration of Ischemic Stroke in Mice
被引:60
作者:

Sakata, Hiroyuki
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机构: Stanford Univ, Neurosurg Labs, Dept Neurosurg, Dept Neurol & Neurol Sci,Sch Med, Stanford, CA 94305 USA

Niizuma, Kuniyasu
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h-index: 0
机构: Stanford Univ, Neurosurg Labs, Dept Neurosurg, Dept Neurol & Neurol Sci,Sch Med, Stanford, CA 94305 USA

Wakai, Takuma
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h-index: 0
机构: Stanford Univ, Neurosurg Labs, Dept Neurosurg, Dept Neurol & Neurol Sci,Sch Med, Stanford, CA 94305 USA

Narasimhan, Purnima
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h-index: 0
机构: Stanford Univ, Neurosurg Labs, Dept Neurosurg, Dept Neurol & Neurol Sci,Sch Med, Stanford, CA 94305 USA

Maier, Carolina M.
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h-index: 0
机构: Stanford Univ, Neurosurg Labs, Dept Neurosurg, Dept Neurol & Neurol Sci,Sch Med, Stanford, CA 94305 USA

Chan, Pak H.
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h-index: 0
机构:
Stanford Univ, Neurosurg Labs, Dept Neurosurg, Dept Neurol & Neurol Sci,Sch Med, Stanford, CA 94305 USA Stanford Univ, Neurosurg Labs, Dept Neurosurg, Dept Neurol & Neurol Sci,Sch Med, Stanford, CA 94305 USA
机构:
[1] Stanford Univ, Neurosurg Labs, Dept Neurosurg, Dept Neurol & Neurol Sci,Sch Med, Stanford, CA 94305 USA
来源:
基金:
美国国家卫生研究院;
关键词:
copper/zinc-superoxide dismutase;
ischemic stroke;
neural stem cell;
neuroprotection;
FOCAL CEREBRAL-ISCHEMIA;
PROTECTS VULNERABLE NEURONS;
TRANSGENIC MICE;
MUTANT MICE;
STEM/PROGENITOR CELLS;
OXIDATIVE STRESS;
SELF-RENEWAL;
INJURY;
DAMAGE;
TRANSPLANTATION;
D O I:
10.1161/STROKEAHA.112.656900
中图分类号:
R74 [神经病学与精神病学];
学科分类号:
摘要:
Background and Purpose-The harsh host brain microenvironment caused by production of reactive oxygen species after ischemic reperfusion injury offers a significant challenge to survival of transplanted neural stem cells (NSCs) after ischemic stroke. Copper/zinc-superoxide dismutase (SOD1) is a specific antioxidant enzyme that counteracts superoxide anions. We have investigated whether genetic manipulation to overexpress SOD1 enhances survival of grafted stem cells and accelerates amelioration of ischemic stroke. Methods-NSCs genetically modified to overexpress or downexpress SOD1 were administered intracerebrally 2 days after transient middle cerebral artery occlusion. Histological and behavioral tests were examined from Days 0 to 28 after stroke. Results-Overexpression of SOD1 suppressed production of superoxide anions after ischemic reperfusion injury and reduced NSC death after transplantation. In contrast, downexpression of SOD1 promoted superoxide generation and increased oxidative stress-mediated NSC death. Transplantation of SOD1-overexpressing NSCs enhanced angiogenesis in the ischemic border zone through upregulation of vascular endothelial growth factor. Moreover, grafted SOD1-overexpressing NSCs reduced infarct size and improved behavioral performance compared with NSCs that were not genetically modified. Conclusions-Our findings reveal a strong involvement of SOD1 expression in NSC survival after ischemic reperfusion injury. We propose that conferring antioxidant properties on NSCs by genetic manipulation of SOD1 is a potential approach for enhancing the effectiveness of cell transplantation therapy in ischemic stroke. (Stroke. 2012;43:2423-2429.)
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页码:2423 / +
页数:19
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机构: Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

Zack, JA
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机构: Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

Kornblum, HI
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机构: Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

Liu, X
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Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

Wu, H
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机构: Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA