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dc.contributor.authorKowalski, Elizabeth A.en
dc.contributor.authorChen, Jiangen
dc.contributor.authorHazy, Amandaen
dc.contributor.authorFritsch, Lauren E.en
dc.contributor.authorGudenschwager-Basso, Erwin K.en
dc.contributor.authorChen, Michaelen
dc.contributor.authorWang, Xiaen
dc.contributor.authorQian, Yunen
dc.contributor.authorZhou, Mingjunen
dc.contributor.authorByerly, Matthewen
dc.contributor.authorPickrell, Alicia M.en
dc.contributor.authorMatson, John B.en
dc.contributor.authorAllen, Irving C.en
dc.contributor.authorTheus, Michelle H.en
dc.date.accessioned2019-11-18T13:02:47Zen
dc.date.available2019-11-18T13:02:47Zen
dc.date.issued2019-11-11en
dc.identifier.citationJournal of Neuroinflammation. 2019 Nov 11;16(1):210en
dc.identifier.urihttp://hdl.handle.net/10919/95564en
dc.description.abstractBackground The continuum of pro- and anti-inflammatory response elicited by traumatic brain injury (TBI) is suggested to play a key role in the outcome of TBI; however, the underlying mechanisms remain ill -defined. Methods Here, we demonstrate that using bone marrow chimeric mice and systemic inhibition of EphA4 receptor shifts the pro-inflammatory milieu to pro-resolving following acute TBI. Results EphA4 expression is increased in the injured cortex as early as 2 h post-TBI and on CX3CR1gfp-positive cells in the peri-lesion. Systemic inhibition or genetic deletion of EphA4 significantly reduced cortical lesion volume and shifted the inflammatory profile of peripheral-derived immune cells to pro-resolving in the damaged cortex. These findings were consistent with in vitro studies showing EphA4 inhibition or deletion altered the inflammatory state of LPS-stimulated monocyte/macrophages towards anti-inflammatory. Phosphoarray analysis revealed that EphA4 may regulate pro-inflammatory gene expression by suppressing the mTOR, Akt, and NF-κB pathways. Our human metadata analysis further demonstrates increased EPHA4 and pro-inflammatory gene expression, which correlates with reduced AKT concurrent with increased brain injury severity in patients. Conclusions Overall, these findings implicate EphA4 as a novel mediator of cortical tissue damage and neuroinflammation following TBI.en
dc.format.mimetypeapplication/pdfen
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titlePeripheral loss of EphA4 ameliorates TBI-induced neuroinflammation and tissue damageen
dc.typeArticle - Refereeden
dc.date.updated2019-11-17T04:20:07Zen
dc.description.versionPublished versionen
dc.rights.holderThe Author(s)en
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentChemistryen
dc.contributor.departmentSchool of Neuroscienceen
dc.contributor.departmentCenter for Drug Discoveryen
dc.title.serialJournal of Neuroinflammationen
dc.identifier.doihttps://doi.org/10.1186/s12974-019-1605-2en
dc.type.dcmitypeTexten


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Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International