GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE319nnn/GSE319914/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319914GEOGSEfalseEndothelial miR-15a/16-1 regulation of Syne1 mediates structural and functional recovery after traumatic brain injuryTraumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and compromises endothelial function, leading to persistent neurological dysfunction. Although miR-15a/16-1 deletion has recently been shown to be neuroprotective in brain injury, the endothelial pathways mediating long-term structural and functional recovery after TBI remain unknown. Here, we demonstrate endothelial-specific deletion of miR-15a/16-1 is sufficient to confer neurorestoration after TBI by reducing acute BBB leakage, preserving white and gray matter integrity, and accelerating sensorimotor and cognitive recovery. Mechanistically, transcriptomic profiling identified Syne1 as a direct downstream target of miR-15a/16-1, validated via in-silico binding prediction and 3’-UTR luciferase assays. Crucially, endothelial cells-targeted AAV-mediated knockdown of Syne1 abrogated the neurorestorative effects of miR-15a/16-1 deletion, indicating Syne1 is required for its function. Furthermore, single-cell RNA-seq analysis of human TBI tissue demonstrates significant downregulation of Syne1 in endothelial cells within the contusion core relative to pericontusional endothelium. Together, these findings define a previously unrecognized miR-15a/16-1–Syne1 axis that governs endothelial repair after TBI, with significant translational potential.2026/08/19GSE319914GSM9529213GSM9529224GSM9529214GSM9529215GSM9529216GSM9529217GSM9529218GSM9529219GSM9529209GSM9529220GSM9529210GSM9529221GSM9529222GSM9529211GSM9529212GSM952922330172319914Mus musculus[42584458]