Blast-induced phenotypic switching in cerebral vasospasm

Area of Science:

• Neuroscience
• Vascular Biology
• Trauma Research

Background:

• Cerebrovasculature vasospasm is a frequent complication of blast-induced traumatic brain injury (bTBI) in combat veterans.
• bTBI-associated vasospasm occurs more frequently and earlier than with other TBI types, even without subarachnoid hemorrhage (SAH).
• The unique mechanics of blast injury are hypothesized to potentiate vasospasm.

Purpose of the Study:

• To investigate if a single rapid mechanical insult can initiate vascular hypercontractility and remodeling, mimicking vasospasm.
• To model the mechanical forces of blast pulses on vasculature using in vitro techniques.
• To elucidate the cellular and molecular mechanisms underlying blast-induced vasospasm.

Main Methods:

• Utilized engineered arterial lamellae subjected to high-velocity stretching to simulate blast pulse mechanics.
• Analyzed intracellular calcium dynamics post-simulated blast injury.
• Assessed vascular smooth muscle cell phenotype and tissue remodeling one day after injury.

Main Results:

• Simulated blast injury induced altered intracellular calcium dynamics, leading to hypersensitivity to endothelin-1 contractile stimulus within one hour.
• One day post-simulated blast, tissues showed blast force-dependent prolonged hypercontraction.
• Evidence of vascular smooth muscle cell phenotype switching and remodeling was observed, indicative of vasospasm initiation.

Conclusions:

• An acute, blast-like mechanical injury is sufficient to initiate vascular hypercontraction.
• This hypercontraction can trigger a genetic switch, promoting vascular remodeling and cerebral vasospasm in bTBI.
• Findings suggest a direct mechanism for vasospasm in bTBI independent of SAH.