Sound-Enhanced Sleep Depth Reduces Traumatic Brain Injury Damage and Sequelae and Supports Microglial Response

Traumatic brain injury significantly reduces the quality of life for millions of survivors worldwide, with no established treatments currently available. High slow-wave activity (SWA) sleep immediately after rodent TBI improves posttraumatic outcomes. However, pharmacological SWA-enhancing strategies are hindered by severe specificity and scalability issues that prevent it from effectively reaching clinical implementation. Alternatively, closed-loop auditory stimulation (CLAS) of sleep slow waves offers specific SWA enhancement with high translational potential. Our present results demonstrate that up-phase-targeted CLAS (upCLAS)-mediated SWA enhancement reduced diffuse axonal injury, decreased demyelination, and preserved cognitive ability in TBI rats. The alleviated posttraumatic phenotype was associated with increased microglia response, likely mediating CLAS neuroprotective effect in the acute injury phase. Auditory-enhanced SWA may thus constitute a novel noninvasive neuroprotective therapy preventing TBI sequelae via boosted cellular response to tissue damage.