The lack of prospective and randomized clinical trials to assess neurological outcomes at different Hb levels severely restricts the ability to make clinical recommendations on how to manage anemic patients in the perioperative setting. Characterization of complex hypoxic cellular mechanisms, including hypoxia inducible factor (HIF), neuronal nitric oxide synthase (nNOS) and erythropoietin (EPO), which are activated in the brain of anemic animals, may provide valuable preclinical information.This will help clinicians to develop treatment strategies to minimize cerebral injury associated with anemia in perioperative patients. For example, clinical studies have suggested that erythropoietin (EPO) therapy may reduce cerebral injury and improve survival in stroke and trauma patients.