Stroke Recovery and Rehabilitation Research: Issues, Opportunities, and the National Institutes of Health StrokeNet.

Stroke is the second leading cause of death and the third leading cause of disability-adjusted life years worldwide. Although numerous therapies have been developed over the past 10 years to treat acute ischemic stroke, the stark reality remains that only 5% of these patients are so treated in the United States,1 in part, because of treatment window times <3 to 6 hours post-onset, and many of these 5% nonetheless have significant long-term disability. Acute treatment options after hemorrhagic stroke remain limited.2 In parallel with efforts to further develop acute stroke interventions, researchers are studying recovery and rehabilitation treatments, which can have a treatment time window measured in days, weeks, or months poststroke. To achieve this goal, therapies aim to maximize function in brain areas that survive the stroke or provide compensatory approaches to improve overall function. Strategies targeting recovery and rehabilitation must be seen as distinct from acute stroke therapies, such as reperfusion or neuroprotection, where the strategy is to limit the severity of ischemic injury, including preserving penumbral tissue and reducing infarct size. Preclinical and translational research have successfully identified numerous molecular and physiological events spontaneously arising in the nervous system during the days-to-weeks after an infarct, and, subsequently, potential restorative therapies that target these events to improve long-term behavioral outcomes.3,4 In parallel, a burgeoning volume of data from human subjects has emerged regarding mechanisms of recovery from stroke. Together, these efforts inform translation into clinical studies for several classes of therapy, including small molecules, growth factors, stem cells, monoclonal antibodies, brain stimulation, robotics and other devices, cognitive strategies, intensive training, and telerehabilitation.5,6 The majority of patients with stroke survive the initial event but go on to live with significant disability for many years. Indeed, there are >7 million stroke survivors …