Over the past decade, the management of acute ischemic stroke has undergone a paradigm shift, especially a longer time-window and a wider indication for endovascular treatments. However, many patients still have long-term dysfunction despite the best medical care at present. Based on findings from innovative proteomic and transcriptomic technologies, researchers have identified an array of novel or previously underappreciated circulatory factors that play pivotal roles in mediating post-injuries brain communication. Thus, the previous concept of the brain as a privileged compartment isolated from the rest of the body has been replaced by the novel consensus that brain bidirectionally interacts with the other organs after brain diseases. In this review, we make a summary of several axes that connect the brain with the rest of the body after stroke. More importantly, we summarize several circulatory factors that play pivotal roles in fostering post-stroke functional recovery in the chronic stage. Special attention is given to the instrumental role of circulatory signals, positing them as significant contributors to the complex process of brain function recovery and as translational therapeutic targets for ischemic stroke in future studies.Copyright © 2025 Elsevier B.V. All rights reserved.