Traumatic Brain Injury Induces Early Barrier Protective Responses in Incisional Skin Wounds Accelerating Cutaneous Wound Healing

Though Traumatic Brain Injury (TBI) and skin trauma often occur together, it is unresolved whether TBI changes healing of skin wounds. We here explored whether TBI impacts on the sequence of events during skin wound healing. Incisional skin wounds from mice subjected to TBI were assessed employing unbiased transcriptome analysis and immunostaining. Transcriptome analysis at day 1 after combined trauma detects a significant enrichment of genes involved in macrophage and T cell recruitment and activation in contrast to skin wounds without TBI. At day 7 after combined trauma, genes in pathways of re-epithelialization including cornification and keratinization and of anti-inflammatory responses were highly enriched. These findings were confirmed by immunostaining with increased re-epithelialisation and cornification and an increased number of macrophages and T cells resolving inflammation. Moreover, the number of dermal myofibroblasts are highly increased in skin wounds after combined trauma. Collectively, TBI enforces an unprecedented defence response with an early onset of enhanced immunity, faster epidermal barrier formation, and a myofibroblast driven acceleration of wounds closure, all together likely counteracting systemic infection. RNA-seq profiling of mouse skin collected from uninjured and wounded skin either from TBI or non-TBI (sham) conditions at day1 and day7 post-TBI.