Timing is everything: Exercise therapy and remote ischemic conditioning for acute ischemic stroke patients

Physical exercise is a promising rehabilitative strategy for acute ischemic stroke. Preclinical trials suggest that exercise restores cerebral blood circulation and re-establishes the blood–brain barrier’s integrity with neurological function and motor skill improvement. Clinical trials demonstrated that exercise improves prognosis and decreases complications after ischemic events. Due to these encouraging findings, early exercise rehabilitation has been quickly adopted into stroke rehabilitation guidelines. Unfortunately, preclinical trials have failed to warn us of an adverse effect. Trials with very early exercise rehabilitation (within 24 h of ischemic attack) found an inferior prognosis at 3 months. It was not immediately clear as to why exercise was detrimental when performed very early while it was ameliorative just a few short days later. This review aimed to explore the potential mechanisms of harm seen in very early exercise administered to acute ischemic stroke patients. To begin, the mechanisms of exercise’s benefit were transposed onto the current understanding of acute ischemic stroke’s pathogenesis, specifically during the acute and subacute phases. Then, exercise rehabilitation’s mechanisms were compared to that of remote ischemic conditioning (RIC). This comparison may reveal how RIC may be providing clinical benefit during the acute phase of ischemic stroke when exercise proved to be harmful.