Abstract WMP80: Enhancement Of Antioxidative Activity Facilitates Neural Stem Cell Transplantation Therapy For Hemorrhagic Stroke
Background: We focused on the effect of oxidative stress against grafted neural stem cells (NSCs) and hypothesized that conferring antioxidant properties to NSCs may overcome cell death in the hostile host environment and enhance neuroprotection after transplantation for hemorrhagic stroke.
Methods: NSCs were obtained from the striatum of copper/zinc-superoxide dismutase transgenic (Tg) mice and wild-type (Wt) mice. The NSCs were exposed to various forms of oxidative stress (hemoglobin, H2O2 and FeCl2). Cell viability and oxidative damage were assessed with WST-1, Live/Dead assay, and hydroethidine (HEt) staining. Intraparenchymal NSC transplantation was performed 3 days after autologous blood was injected into mouse striatum for NSC efficacy after transplantation. We performed 8-hydroxyguanosine (8-OHG) staining 4 hours after transplantation to assess oxidative damage in the grafted NSCs. Striatum size was measured to evaluate atrophy, and surviving neurons in the striatum were counted 35 days after hemorrhagic insult. Neurological evaluation was performed 1, 3, 7, 14, 21, 28, and 35 days after hemorrhagic insult.
Results: Cell viability of Tg NSCs was significantly increased compared with Wt NSCs. Both HEt and 8-OHG signals were suppressed in Tg NSCs. Tg NSC transplantation showed a significant reduction in striatum atrophy (86±3% vs 82±4%, n=7, p<0.05, striatum size/contralateral) and showed an increase in surviving neurons in the striatum (73±12% vs 57±12%, n=6, p<0.05, number of neurons/contralateral) compared with Wt NSC transplantation. In the Tg group, progressive improvement was observed 35 days after hemorrhagic insult compared with the Wt group (n=9, p<0.05).
Conclusion: Our results suggest that enhanced antioxidative activity in NSCs improves efficacy of stem cell therapy for the hemorrhagic stroke brain.
- © 2012 by American Heart Association, Inc.