Enhancing muscle and brain resilience: The role of prehabilitative exercise in mitigating disuse effects

Short-term disuse leads to rapid declines in muscle mass and strength. These declines are driven by changes at all levels of the neuromuscular system; the brain, spinal cord and skeletal muscle. In addition to neural input from the central and peripheral nervous systems to the muscle, molecular factors originating in the muscle can be transported to the central nervous system. These interactions highlight the interconnected nature of the neuromuscular system during exercise and disuse, and form the basis for this review. Although it is well known that physical activity confers a myriad of health benefits, a recent interest in targeted exercise before periods of disuse or immobility, termed prehabilitation, has emerged. Clinical studies within multiple medical specialities suggest positive effects of prehabilitative exercise on preserving muscle function, reducing adverse outcomes and shortening the length of hospital stay. Yet, the studies available are few and heterogeneous, and the underlying protective mechanisms of prehabilitative exercise remain elusive. In this review, we examine the ramifications of disuse across all levels of the neuromuscular system and explore how prehabilitation may counteract these effects. We summarize these mechanisms into three primary categories: (1) enhancing pre-disuse capacity; (2) establishing neural and muscle memory; and (3) fostering structural adaptations in both muscle and brain.