Remote ischemic conditioning with exercise (RICE) promotes functional rehabilitation following ischemic stroke

Abstract

ABSTRACT Objective: Exercise is an essential rehabilitative strategy after stroke butits implementation is limited as its very early use can exacerbate damage and is restricted by patient disability. Remote Ischemic Conditioning (RIC) is a safe alternative for post-stroke neuroprotetion. The present study investigated the neurorehabilitative benefits of early RIC followed by exercise (RICE) therapy. Methods: 48 adult male Sprague–Dawley rats were divided into groups: 1) sham, 2) stroke, 3) stroke with RICE at day 3 (RIC 6 hours after reperfusion followed by exercise days 3 to 28), 4) stroke with exercise at day 3 (exercise days 3 to 28), and 5) stroke with RICE at day 1 (RIC 6 hours after reperfusion followed by exercise days 1 to 28), 6) stroke with exercise at day 1 (exercise days 1 to 28 after reperfusion). Long-term functional outcomes were determined by grid walk, rota-rod, adhesive tape touch, and Morris water maze. Levels of mRNA and proteins of neuroplasticity, synaptogenesis, and angiogenesis, were determined. Results: As compared to exercise only, animals that underwent RICE had significant improvements in functional outcomes after stroke. These improvements were most significant in groups that had the later initiation of exercise. In addition, all treatment groups showed significant increases in mRNA and protein expression of the target molecules for neuroplasticity, synaptogenesis, and angiogenesis, while further significant increases were observed after RICE following ischemic stroke. Conclusions: RICE, a novel therapy that supplements RIC prior to exercise, is superiorly effective in inducing rehabilitation after stroke as compared to the traditional exercise monotherapy rehabilitation in rats with ischemic brain injury.