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Updated: Mar 27, 2026
Author Spotlight: Deciphering the Long-Term Effects of Low-Level Blast Exposures in Mice
Published on: May 24, 2024
Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction
B R Huber1, J S Meabon2, Z S Hoffer3
1VA Jamaica Plain, Department of Neurology, Boston University School of Medicine, Jamaica Plain, MA, USA.
Abstract:
Exposure to blast overpressure (BOP) is associated with behavioral, cognitive, and neuroimaging abnormalities. We investigated the dynamic responses of cortical vasculature and its relation to microglia/macrophage activation in mice using intravital two-photon microscopy following mild blast exposure. We found that blast caused vascular dysfunction evidenced by microdomains of aberrant vascular permeability. Microglial/macrophage activation was specifically associated with these restricted microdomains, as evidenced by rapid microglial process retraction, increased ameboid morphology, and escape of blood-borne Q-dot tracers that were internalized in microglial/macrophage cell bodies and phagosome-like compartments. Microdomains of cortical vascular disruption and microglial/macrophage activation were also associated with aberrant tight junction morphology that was more prominent after repetitive (3×) blast exposure. Repetitive, but not single, BOPs also caused TNFα elevation two weeks post-blast. In addition, following a single BOP we found that aberrantly phosphorylated tau rapidly accumulated in perivascular domains, but cleared within four hours, suggesting it was removed from the perivascular area, degraded, and/or dephosphorylated. Taken together these findings argue that mild blast exposure causes an evolving CNS insult that is initiated by discrete disturbances of vascular function, thereby setting the stage for more protracted and more widespread neuroinflammatory responses.
Insights
Mild blast exposure triggers brain vascular dysfunction and microglia activation. These initial insults, especially after repeated blasts, may lead to long-term neuroinflammation and cognitive deficits.
Area of Science:
- Neuroscience
- Vascular Biology
- Neuroinflammation
Background:
- Blast overpressure (BOP) exposure is linked to behavioral, cognitive, and neuroimaging abnormalities.
- Understanding the immediate cellular and molecular responses in the brain following BOP is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the dynamic responses of cortical vasculature and its relationship with microglia/macrophage activation after mild blast exposure in mice.
Main Methods:
- Intravital two-photon microscopy was used to observe dynamic changes in the mouse brain cortex following mild blast exposure.
- Assessment of vascular permeability, microglial/macrophage morphology and activation, tight junction integrity, and phosphorylated tau accumulation.
Main Results:
- Mild blast exposure induced localized vascular dysfunction with aberrant permeability.
- Microglial/macrophage activation, characterized by process retraction and ameboid morphology, was spatially associated with vascular disruptions.
- Repetitive blasts exacerbated vascular and tight junction abnormalities and led to elevated TNFα levels two weeks post-exposure.
- Aberrantly phosphorylated tau accumulated in perivascular domains after a single blast but was cleared within four hours.
Conclusions:
- Mild blast exposure initiates a cascade of central nervous system (CNS) injury, beginning with discrete vascular disturbances.
- These vascular changes facilitate subsequent neuroinflammatory responses involving microglia/macrophage activation.
- Repetitive blast exposures may lead to more severe and persistent neuroinflammatory consequences.
