Semaphorin 3A promotes resilience of sleep and cognition to brain injury

Abstract

Chronic sleep disruption and cognitive deficits are debilitating long-term consequences of traumatic brain injury (TBI), yet the endogenous mechanisms that drive network-level recovery remain poorly understood. Here, we demonstrate that during the chronic phase post-injury, network oscillations critical for memory, including slow oscillations, delta waves, and sleep spindles, undergo precise adaptive tuning that sustains sleep-dependent memory consolidation. This functional circuit resilience requires Semaphorin-3A (Sema3a); loss of Sema3a function prevents the protective reorganization of non-rapid eye movement (NREM) sleep architecture, impairs sleep-dependent memory consolidation, and exacerbates cortical lesion size. Together, these findings identify Sema3a as an innate protective mechanism that preserves sleep architecture and cognitive function following TBI.