REPRINT: International, multicenter randomized preclinical trials in translational stroke research: It is time to act

摘要

Over the last decades, tremendous progress has been made in our understanding of the vascular, cellular, and molecular mechanisms leading to brain tissue injury after ischemic stroke. This research has exposed numerous potential targets to intercept the cascades of ischemic damage (Vosler and Chen 2009). This promise of "neuroprotection" has been an important potential therapeutic consideration in the cerebral ischemia field ever since the discovery of "excitotoxic" mechanisms of cell death in experimental models of stroke in the 1980s. Experiments in rodents demonstrated that the focally ischemic brain can indeed be protected pharmacologically, reducing infarction and improving functional outcome. However, so far every attempt to translate this preclinical success into clinically effective therapies has failed (Endres et al 2008). The very recent failure of the AX200 for the Treatment of Ischemic Stroke (AXIS) 2 trial, investigating treatment with the hematopoetic cytokine granulocyte colony-stimulating factor in acute ischemic stoke (Sygnis 2011), has further reinforced the apparent translational roadblock. Translational stroke research is in a crisis, and pharmaceutical companies continue to exit the field.