Citation

Alford PW, Dabiri BE, Goss JA, Hemphill MA, Brigham MD, Parker KK. Proc. Natl. Acad. Sci. U. S. A. 2011; 108(31): 12705-12710.

Affiliation

Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard School of Engineering and Applied Science, Pierce Hall #321, 29 Oxford Street, Cambridge, MA 02138.

Copyright

(Copyright © 2011, National Academy of Sciences)

DOI

10.1073/pnas.1105860108

PMID

21765001

PMCID

PMC3150891

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.

Language: en