Abstract WP94: Delayed SDF-1 Hyperexpression Promotes Neural Stem Cell Migration and Maturation without Increasing Inflammation after Ischemic Stroke in Mice
Background and purpose: SDF-1 has double-edged function after ischemic stroke. It can attract both inflammatory cells and neural stem cells (NSC). However, the action of SDF-1 in regulating neural stem cells migration and maturation during post-ischemic stroke is unclear. Here we used adeno-associated virus (AAV) to deliver SDF-1 gene into the peri-infarct area one week after permanent middle cerebral artery occlusion (MCAO) to investigate the effect of SDF-1 on endogenous NSC migration and maturation.
Methods and materials: Twenty-four adult ICR male mice received AAV carrying SDF-1 or GFP gene transfer into the peri-infarct area one week after MCAO. Brain atrophy volume, neurobehavioral tests and immunohistochemistry were performed to evaluate the effects of SDF-1 on endogenous NSC migration, maturation and neuronal function repair.
Results: SDF-1 was highly expressed in peri-infarct area for at least four weeks after gene transfer. Brain atrophy volume was significantly reduced in AAV-SDF-1 group compared to AAV-GFP gourp (p<0.05). The results of neurobehavioral tests including neurological deficits and rotarod test paralleled the result of atrophy volume, with neuronal function greatly improved in AAV-SDF-1 group (p<0.05). Immunohistology showed that the number of nestin and doublecortin positive cells in peri-infarct area was significantly increased in AAV-SDF-1 group in contrast to AAV-GFP group (p<0.05). In addition, there was no difference in myeloperoxidase positive cells in ischemic peri-infarct area between AAV-SDF-1 and AAV-GFP group (p>0.05).
Conclusion: Our results demonstrated that SDF-1 gene therapy significantly increased NSC migration and maturation without increasing focal inflammatory response; consequently reduced brain atrophy volume and improved the neurological outcomes of animals, suggesting that delayed SDF-1 hyperexpression plays a key role in neurogenesis and neural repair. These in vivo results indicate that SDF-1 holds great potential as a stem cell chemotactic factor in the treatment of ischemic stroke.
- © 2012 by American Heart Association, Inc.