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

Area of Science:

• Neuroscience
• Traumatic Brain Injury Research
• Biomedical Engineering

Background:

• Preclinical blast studies show brain tissue damage across various overpressures and exposure durations.
• Limited research exists on low-intensity, short-duration primary blast effects in the sub-millisecond range, particularly subclinical blast.
• Understanding subclinical blast is crucial for animal model scaling and assessing effects of small arms fire and munitions.

Purpose of the Study:

• To investigate neurovascular outcomes following low-level, sub-millisecond duration primary blast exposure.
• To characterize the effects of putatively subclinical blast on brain microvasculature.
• To assess the vulnerability of the brain's microvasculature to short-duration, low-intensity blast waves.

Main Methods:

• Utilized a characterized model of subclinical low-level primary blast with sub-millisecond duration overpressure.
• Employed Computational Fluid Dynamics (CFD) to model and minimize turbulent flow effects.
• Examined neurovascular outcomes, including perivascular S100β expression, sodium fluorescein leakage, and MMP9/VEGF expression, at <12 kPa overpressure.

Main Results:

• Short duration subclinical blast significantly reduced perivascular S100β expression compared to controls.
• Demonstrated evidence of neurovascular disruption through sodium fluorescein leakage.
• Observed increased expression of matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF).

Conclusions:

• The brain's microvasculature is vulnerable to low-intensity, short-duration blast exposure, even at putatively subclinical levels.
• Findings challenge the notion that only higher intensity blasts cause significant neurovascular damage.
• This research underscores the importance of considering blast duration and intensity in preclinical models and understanding wartime blast exposure effects.