Blast-induced phenotypic switching in cerebral vasospasm

Patrick W. Alford, Borna E. Dabiri, Josue A. Goss, Matthew A. Hemphill, Mark D. Brigham, Kevin Kit Parker

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Vasospasm 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.

Original languageEnglish (US)
Pages (from-to)12705-12710
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number31
DOIs
StatePublished - Aug 2 2011

Keywords

  • Mechanotransduction
  • Neurotrauma
  • Tissue engineering
  • Vascular mechanics

Fingerprint Dive into the research topics of 'Blast-induced phenotypic switching in cerebral vasospasm'. Together they form a unique fingerprint.

Cite this