Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury

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dc.contributor.authorHazy, Amandaen
dc.contributor.authorBochicchio, Laurenen
dc.contributor.authorOliver, Andreaen
dc.contributor.authorXie, Ericen
dc.contributor.authorGeng, Shuoen
dc.contributor.authorBrickler, Thomasen
dc.contributor.authorXie, Hehuang Daviden
dc.contributor.authorLi, Liwuen
dc.contributor.authorAllen, Irving C.en
dc.contributor.authorTheus, Michelle H.en
dc.contributor.departmentCenter for Veterinary Regenerative Medicineen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentStatisticsen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.contributor.departmentSchool of Neuroscienceen
dc.date.accessioned2019-07-23T16:50:04Zen
dc.date.available2019-07-23T16:50:04Zen
dc.date.issued2019-06-12en
dc.description.abstractThe peripheral immune system is a major regulator of the pathophysiology associated with traumatic brain injury (TBI). While age-at-injury influences recovery from TBI, the differential effects on the peripheral immune response remain unknown. Here, we investigated the effects of TBI on gene expression changes in murine whole blood using RNAseq analysis, gene ontology and network topology-based key driver analysis. Genome-wide comparison of CCI-injured peripheral whole blood showed a significant increase in genes involved in proteolysis and oxidative-reduction processes in juvenile compared to adult. Conversely, a greater number of genes, involved in migration, cytokine-mediated signaling and adhesion, were found reduced in CCI-injured juvenile compared to CCI-injured adult immune cells. Key driver analysis also identified G-protein coupled and novel pattern recognition receptor (PRR), P2RY10, as a central regulator of these genes. Lastly, we found Dectin-1, a c-type lectin PRR to be reduced at the protein level in both naive neutrophils and on infiltrating immune cells in the CCI-injured juvenile cortex. These findings demonstrate a distinct peripheral inflammatory profile in juvenile mice, which may impact the injury and repair response to brain trauma.en
dc.description.notesThis work was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, R01NS096281 (MHT). We recognize the Regenerative Medicine-Interdisciplinary Graduate Education Program at Virginia Tech and The Institute of Critical Technology and Applied Sciences Programs for student support (TB, AH), The Center for Engineered Health and the Virginia-Maryland College of Veterinary Medicine.en
dc.description.sponsorshipNational Institute of Neurological Disorders and Stroke of the National Institutes of Health [R01NS096281]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-019-45089-zen
dc.identifier.issn2045-2322en
dc.identifier.other8564en
dc.identifier.pmid31189983en
dc.identifier.urihttp://hdl.handle.net/10919/91921en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectsubventricular zoneen
dc.subjectenrichment analysisen
dc.subjecthead-injuryen
dc.subjectinflammationen
dc.subjectreceptorsen
dc.subjectcnsen
dc.subjectdectin-1en
dc.subjectneuroprotectionen
dc.subjectincreasesen
dc.subjectgenecodisen
dc.titleDivergent age-dependent peripheral immune transcriptomic profile following traumatic brain injuryen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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