Exploring and exploiting unique properties of the hippocampal dentate gyrus for post-stroke therapy: astrocytes link ischemic resistance with neurogenic potential.

Abstract

Acute cerebral ischemia can occur secondary to embolism, cardiac arrest, hemorrhage, traumatic brain injury, edema, vascular compression, or any physiologic condition resulting in low cardiac output state. Survivors of cerebral ischemic events frequently suffer from profound disability, accounting for > $70 billion in 2010 for treatment of embolic stroke in the US alone. More strikingly, the cost to treat stroke in the US is anticipated to soar to > $180 billion by 2030, according to estimates from the American Heart Association (Ovbiagele et al., 2013). Despite hundreds of promising pre-clinical studies in animal models, effective clinical treatments for the most common forms of cerebral ischemia remain limited: standard treatment for embolic stroke is restricted to thrombolytic therapy or clot retrieval during a narrow therapeutic window, while post-resuscitation treatment following cardiac arrest remains the (controversial) application of mild hypothermia. The massive failure to translate experimental findings to the development of any successful clinical intervention suggests that redirecting investigational resources to developing new therapies to improve long-term recovery in survivors of stroke may be a logical and necessary next step.