Neural stem cell therapies and hypoxic-ischemic brain injury.

Hypoxic-ischemic brain injury is a significant cause of morbidity and mortality in the adult as well as in the neonate. Extensive pre-clinical studies have shown promising therapeutic effects of neural stem cell-based treatments for hypoxic-ischemic brain injury. There are two major strategies of neural stem cell-based therapies: transplanting exogenous neural stem cells and boosting self-repair of endogenous neural stem cells. Neural stem cell transplantation has been proved to improve functional recovery after brain injury through multiple by-stander mechanisms (e.g., neuroprotection, immunomodulation), rather than simple cell-replacement. Endogenous neural stem cells reside in certain neurogenic niches of the brain and response to brain injury. Many molecules (e.g., neurotrophic factors) can stimulate or enhance proliferation and differentiation of endogenous neural stem cells after injury. In this review, we first present an overview of neural stem cells during normal brain development and the effect of hypoxic-ischemic injury on the activation and function of endogenous neural stem cells in the brain. We then summarize and discuss the current knowledge of strategies and mechanisms for neural stem cell-based therapies on brain hypoxic-ischemic injury, including neonatal hypoxic-ischemic brain injury and adult ischemic stroke.