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

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)441-449
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume34
Issue number3
DOIs
Publication statusPublished - 2014 Mar

Keywords

  • cell transplantation therapy
  • copper/zinc-superoxide dismutase
  • intracerebral hemorrhage
  • neural stem cell
  • reactive oxygen species

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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