Towards reperfusion-centric preclinical stroke research: outside the box of "reperfusion injury".

Abstract

Stroke is a major health issue of increasing significance for any society with an aging population. Globally, stroke is the second-leading cause of death with approximately 5.9 million fatal events in 2010, equivalent to 11.1% of all deaths. Yet, despite years of preclinical research on neuroprotection and a multitude of clinical trials, tissue plasminogen activator (tPA)-mediated recanalization remains the mainstay of acute ischemic stroke therapy, whereas tPA thrombolysis rarely provides benefits in the mechanical occlusion-based stroke models. This split between the bench and bedside raised the concern over the clinical applicability of neuroprotection in acute ischemic stroke. In this perspective commentary, we call for attention to the differences between mechanical-occlusion and thromboembolic stroke models in cerebral hemodynamics (Figure ​Figure1A,1A, ​,BB), the implications of these differences in view of progressive pathobiology of ischemic stroke (Figure 1C), and the need and strategies towards reperfusion-centric preclinical stroke research.