Atherogenic-like lesions associated with a progressive chronic vascular degeneration in a rat model of repetitive low-level blast brain injury.

Repetitive low-level blast exposures in rats induce the development of a post-traumatic stress disorder (PTSD)-like phenotype and evolving chronic brain vascular alterations. These alterations included atherogenic-like lesions characterized by increased extravasation of blood elements into the arterial subendothelial layers, nuclear expression of c-Fos in endothelial and vascular smooth muscle cells, vascular hyperplasia, foam cell formation, and ultimately vascular rupture. Foam cells were mainly of macrophage/microglial or of vascular smooth muscle cell origin with upregulated expression of MHC II and of its co-stimulatory molecule CD86, which is characteristic of antigen-presenting cells. Foam cells also upregulated the lysosomal CD68 marker, indicating macrophage/microglial phagocytic and inflammatory activity. Foam cells of vascular smooth muscle cell origin were present at arteriolar bends, kinks, and bifurcations and were associated with a progressive arterial network degeneration in regions with enlarged perivascular spaces. Foam cell inclusions also contained the gelatinase MMP-9, which is involved in extracellular matrix degradation, and the pro-inflammatory cytokine TNF-α that further induces foam cell formation. These findings indicate that the chronic atherogenic lesions associated with blast-induced vascular degeneration may trigger a progressive pro-inflammatory state and expand the progressive vascular degeneration associated with the PTSD-like phenotype.