Background　Traumatic　brain　injury　(TBI)　leads　to　cell　and　tissue　impairment,　as　well　as　functional　deficits.　Stem　cells　promote　structural　and　functional　recovery　and　thus　are　considered　as　a　promising　therapy　for　various　nerve　injuries.　Here,　we　aimed　to　investigate　the　role　of　ectoderm-derived　frontal　bone　mesenchymal　stem　cells　(FbMSCs)　in　promoting　cerebral　repair　and　functional　recovery　in　a　murine　TBI　model.　Methods　A　murine　TBI　model　was　established　by　injuring　C57BL/6　N　mice　with　moderate-controlled　cortical　impact　to　evaluate　the　extent　of　brain　damage　and　behavioral　deficits.　Ectoderm-derived　FbMSCs　were　isolated　from　the　frontal　bone　and　their　characteristics　were　assessed　using　multiple　differentiation　assays,　flow　cytometry　and　microarray　analysis.　Brain　repairment　and　functional　recovery　were　analyzed　at　different　days　post-injury　with　or　without　FbMSC　application.　Behavioral　tests　were　performed　to　assess　learning　and　memory　improvements.　RNA　sequencing　analysis,　immunofluorescence　staining,　and　quantitative　reverse-transcription　polymerase　chain　reaction　(qRT-PCR)　were　used　to　examine　inflammation　reaction　and　neural　regeneration.　In　vitro　co-culture　analysis　and　quantification　of　glutamate　transportation　were　carried　out　to　explore　the　possible　mechanism　of　neurogenesis　and　functional　recovery　promoted　by　FbMSCs.　Results　Ectoderm-derived　FbMSCs　showed　fibroblast　like　morphology　and　osteogenic　differentiation　capacity.　FbMSCs　were　CD105,　CD29　positive　and　CD45,　CD31　negative.　Different　from　mesoderm-derived　MSCs,　FbMSCs　expressed　the　ectoderm-specific　transcription　factor　Tfap2　beta.　TBI　mice　showed　impaired　learning　and　memory　deficits.　Microglia　and　astrocyte　activation,　as　well　as　neural　damage,　were　significantly　increased　post-injury.　FbMSC　application　ameliorated　the　behavioral　deficits　of　TBI　mice　and　promoted　neural　regeneration.　RNA　sequencing　analysis　showed　that　signal　pathways　related　to　inflammation　decreased,　whereas　those　related　to　neural　activation　increased.　Immunofluorescence　staining　and　qRT-PCR　data　revealed　that　microglial　activation　and　astrocyte　polarization　to　the　A1　phenotype　were　suppressed　by　FbMSC　application.　In　addition,　FGF1　secreted　from　FbMSCs　enhanced　glutamate　transportation　by　astrocytes　and　alleviated　the　cytotoxic　effect　of　excessive　glutamate　on　neurons.　Conclusions　Ectoderm-derived　FbMSC　application　significantly　alleviated　neuroinflammation,　brain　injury,　and　excitatory　toxicity　to　neurons,　improved　cognition　and　behavioral　deficits　in　TBI　mice.　Therefore,　ectoderm-derived　FbMSCs　could　be　ideal　therapeutic　candidates　for　TBI　which　mostly　affect　cells　from　the　same　embryonic　origins　as　FbMSCs.