Transplantation of neural stem cells that overexpress SOD1 enhances amelioration of intracerebral hemorrhage in mice

Takuma Wakai, Hiroyuki Sakata, Purnima Narasimhan, Hideyuki Yoshioka, Hiroyuki Kinouchi, Pak H. Chan

研究成果: Article査読

20 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)441-449
ページ数9
ジャーナルJournal of Cerebral Blood Flow and Metabolism
34
3
DOI
出版ステータスPublished - 2014 3

ASJC Scopus subject areas

  • 神経学
  • 臨床神経学
  • 循環器および心血管医学

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