Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model

dc.contributor.authorHubbard, W. Braden
dc.contributor.authorLashof-Sullivan, Margareten
dc.contributor.authorGreenberg, Shaylenen
dc.contributor.authorNorris, Carlyen
dc.contributor.authorEck, Josephen
dc.contributor.authorLavik, Erinen
dc.contributor.authorVandeVord, Pamela J.en
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.date.accessioned2018-12-12T20:05:53Zen
dc.date.available2018-12-12T20:05:53Zen
dc.date.issued2018-07-13en
dc.description.abstractExplosions account for 79% of combat related injuries and often lead to polytrauma, a majority of which include blast-induced traumatic brain injuries (bTBI). These injuries lead to internal bleeding in multiple organs and, in the case of bTBI, long term neurological deficits. Currently, there are no treatments for internal bleeding beyond fluid resuscitation and surgery. There is also a dearth of treatments for TBI. We have developed a novel approach using hemostatic nanoparticles that encapsulate an anti-inflammatory, dexamethasone, to stop the bleeding and reduce inflammation after injury. We hypothesize that this will improve not only survival but long term functional outcomes after blast polytrauma. Poly(lactic-co-glycolic acid) hemostatic nanoparticles encapsulating dexamethasone (hDNPs) were fabricated and tested following injury along with appropriate controls. Rats were exposed to a single blast wave using an Advanced Blast Simulator, inducing primary blast lung and bTBI. Survival was elevated in the hDNPs group compared to controls. Elevated anxiety parameters were found in the controls, compared to hDNPs. Histological analysis indicated that apoptosis and blood-brain barrier disruption in the amygdala were significantly increased in the controls compared to the hDNPs and sham groups. Immediate intervention is crucial to mitigate injury mechanisms that contribute to emotional deficits.en
dc.description.notesWe would like to thank Dr. Michael Urban, Dr. Zachary Bailey, Bryce Dunn, and Ryan Brady for their technical assistance during blast testing. We would like to acknowledge funding support by the DOD CDMRP Program W81XWH-11-1-0014 and the NIH Director's New Innovator Award number DP20D007338 (EL).en
dc.description.sponsorshipDOD CDMRP Program [W81XWH-11-1-0014]; NIH Director's New Innovator Award [DP20D007338]en
dc.format.extent12 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-018-28848-2en
dc.identifier.issn2045-2322en
dc.identifier.other10622en
dc.identifier.pmid30006635en
dc.identifier.urihttp://hdl.handle.net/10919/86353en
dc.identifier.volume8en
dc.language.isoen_USen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectblood-brain-barrieren
dc.subjectposttraumatic-stress-disorderen
dc.subjectpsychiatric-disordersen
dc.subjectoxidative stressen
dc.subjectlung injuryen
dc.subjectspinal-corden
dc.subjectmouse modelen
dc.subjecttime-courseen
dc.subjectopen-fielden
dc.subjectrat modelen
dc.titleHemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma modelen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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