Improved stroke care has resulted in greater survival, but >50 % of patients have chronic disabilities and 33 % are institutionalized. While stroke rehabilitation is helpful, recovery is limited and the most significant gains occur in the first 2–3 months. Stroke triggers an early wave of gene and protein changes, many of which are potentially beneficial for recovery. It is likely that these molecular changes are what subserve spontaneous recovery. Two interventions, aerobic exercise and environmental enrichment, have pleiotropic actions that influence many of the same molecular changes associated with stroke injury and subsequent spontaneous recovery. Enrichment paradigms have been used for decades in adult and neonatal animal models of brain injury and are now being adapted for use in the clinic. Aerobic exercise enhances motor recovery and helps reduce depression after stroke. While exercise attenuates many of the signs associated with normal aging (e.g., hippocampal atrophy), its ability to reverse cognitive impairments subsequent to stroke is less evident. It may be that stroke, like other diseases such as cancer, needs to use multimodal treatments that augment complimentary neurorestorative processes.Electronic supplementary materialThe online version of this article (doi:10.1007/s13311-016-0423-9) contains supplementary material, which is available to authorized users.
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