Stroke is a leading cause of disability and death, yet effective treatments for acute stroke has been very limited. Thus far, tissue plasminogen activator has been the only FDA-approved drug for thrombolytic treatment of ischemic stroke patients, yet its application is only applicable to less than 4-5% of stroke patients due to the narrow therapeutic window (< 4.5 hours after the onset of stroke) and the high risk of hemorrhagic transformation. Emerging evidence from basic and clinical studies has shown that therapeutic hypothermia, also known as targeted temperature management, can be a promising therapy for patients with different types of stroke. Moreover, the success in animal models using pharmacologically induced hypothermia (PIH) has gained increasing momentum for clinical translation of hypothermic therapy. This review provides an updated overview of the mechanisms and protective effects of therapeutic hypothermia, as well as the recent development and findings behind PIH treatment. It is expected that a safe and effective hypothermic therapy has a high translational potential for clinical treatment of patients with stroke and other CNS injuries.
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 1]A, B), the implications of these differences in view of progressive pathobiology of ischemic stroke ([Figure 1]C), and the need and strategies towards reperfusion-centric preclinical stroke research.