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dc.contributor.authorAlford, Patrick W.
dc.contributor.authorDabiri, Borna Esfahani
dc.contributor.authorGoss, Josue
dc.contributor.authorHemphill, Matthew Allen
dc.contributor.authorBrigham, Mark Daniel
dc.contributor.authorParker, Kevin Kit
dc.date.accessioned2015-08-10T17:02:15Z
dc.date.issued2011
dc.identifier.citationAlford, P. W., B. E. Dabiri, J. A. Goss, M. A. Hemphill, M. D. Brigham, and K. K. Parker. 2011. “Blast-Induced Phenotypic Switching in Cerebral Vasospasm.” Proceedings of the National Academy of Sciences 108 (31) (July 15): 12705–12710. doi:10.1073/pnas.1105860108.en_US
dc.identifier.issn0027-8424en_US
dc.identifier.issn1091-6490en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:17985224
dc.description.abstractVasospasm of the cerebrovasculature is a common manifestation of blast-induced traumatic brain injury (bTBI) reported among combat casualties in the conflicts in Afghanistan and Iraq. Cerebral vasospasm occurs more frequently, and with earlier onset, in bTBI patients than in patients with other TBI injury modes, such as blunt force trauma. Though vasospasm is usually associated with the presence of subarachnoid hemorrhage (SAH), SAH is not required for vasospasm in bTBI, which suggests that the unique mechanics of blast injury could potentiate vasospasm onset, accounting for the increased incidence. Here, using theoretical and in vitro models, we show that a single rapid mechanical insult can induce vascular hypercontractility and remodeling, indicative of vasospasm initiation. We employed high-velocity stretching of engineered arterial lamellae to simulate the mechanical forces of a blast pulse on the vasculature. An hour after a simulated blast, injured tissues displayed altered intracellular calcium dynamics leading to hypersensitivity to contractile stimulus with endothelin-1. One day after simulated blast, tissues exhibited blast force dependent prolonged hypercontraction and vascular smooth muscle phenotype switching, indicative of remodeling. These results suggest that an acute, blast-like injury is sufficient to induce a hypercontraction-induced genetic switch that potentiates vascular remodeling, and cerebral vasospasm, in bTBI patients.en_US
dc.description.sponsorshipEngineering and Applied Sciencesen_US
dc.language.isoen_USen_US
dc.publisherProceedings of the National Academy of Sciencesen_US
dc.relation.isversionofdoi:10.1073/pnas.1105860108en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pubmed/21765001en_US
dash.licenseLAA
dc.subjectneurotraumaen_US
dc.subjectmechanotransductionen_US
dc.subjecttissue engineeringen_US
dc.subjectvascular mechanicsen_US
dc.titleBlast-induced phenotypic switching in cerebral vasospasmen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dash.depositing.authorParker, Kevin Kit
dash.waiver2011-06-27
dc.date.available2015-08-10T17:02:15Z
dc.identifier.doi10.1073/pnas.1105860108*
dash.contributor.affiliatedHemphill, Matthew Allen
dash.contributor.affiliatedDabiri, Borna
dash.contributor.affiliatedBrigham, Mark Daniel
dash.contributor.affiliatedGoss, Josue
dash.contributor.affiliatedParker, Kevin


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