Short-duration, low-level subclinical primary blast induces neurovascular compromise, and increased MMP9 expression.

Preclinical blast studies to date have demonstrated pathological changes to brain tissue over a range of overpressures and duration of exposure. While there is evidence of vascular leakage in some reports, there are few reports examining low-intensity, short duration primary blast in the sub-millisecond range. Specifically, subclinical blast has received little scrutiny in blast models but remains an important aspect of wartime blast exposure. Low-level, short duration blasts have important implications regarding the scaling of blast exposure in small animal test subjects as well as understanding the effects of short duration shockwaves from small arms fire and military training with munitions. Here we employed the use of a previously characterized model of subclinical low-level primary blast with sub-millisecond duration overpressure. We used a CFD model to characterize the turbulent flow effects in our experimental model and to confirm that these effects on the target were minimal. There was good correlation between predicted and experimental pressure values. We examined neurovascular outcomes in subclinical blast at < 12 k Pa overpressure and sub-millisecond duration. Short duration subclinical blast resulted in a significant loss of perivascular S100β expression compared to controls. Evidence of neurovascular disruption was demonstrated by sodium fluorescein leakage as well as increased expression of MMP9 and VEGF. While animal studies have not focused on blast duration and intensity in this putatively subclinical range, our results taken collectively demonstrate that the microvasculature of the brain is indeed vulnerable to these doses.