Sleep and Circadian Regulation of Neural Repair and Plasticity after Central Nervous System Injury

Abstract

Neural repair and plasticity after central nervous system injury depend on tightly coordinated biological processes, including synaptic remodelling, adult neurogenesis, metabolic clearance, and immune regulation. Sleep and circadian rhythms have emerged as key modulators of these processes, yet they remain under integrated within prevailing models of neural recovery. This review evaluates experimental and clinical evidence linking sleep and circadian biology to neural repair following stroke, traumatic brain injury, and related conditions. We examine how sleep disruption impairs synaptic plasticity, glymphatic clearance, and functional recovery, and how circadian clocks regulate neural stem cell dynamics and neuroinflammatory responses. Methodological strengths and limitations across studies are analysed, with emphasis on inconsistencies arising from heterogeneous injury models, sleep paradigms, and outcome measures. Studies reveal convergent evidence that temporal misalignment exacerbates secondary injury, although effect sizes vary widely. We identify critical gaps, including the failure to disentangle sleep dependent from circadian dependent mechanisms and the under representation of sex and age as biological variables. Finally, we discuss emerging therapeutic strategies targeting sleep and circadian pathways and propose research directions to integrate chronobiology into neural repair paradigms.