Chronic Neurovascular Degeneration After Repetitive Low-Level Blast Exposure

Gama Sosa MA, De Gasperi R, Pryor D, Perez Garcia GS, Perez GM, Abutarboush R, Kawoos U, Hogg S, Ache B, Sowa A, Tetreault T, Varghese M, Cook DG, Zhu CW, Tappan SJ, Janssen WGM, Hof PR, Ahlers ST, Elder GA. Late chronic local inflammation, synaptic alterations, vascular remodeling and arteriovenous malformations in the brains of male rats exposed to repetitive low-level blast overpressures. Acta Neuropathol Commun 2023;11(1):81. doi: 10.1186/s40478-023-01553-6. 

Background: Repetitive low-level blast exposure has been linked to long-term neurological and vascular damage contributing to behavioral and cognitive deficits resembling post-traumatic stress disorder. Previous work identified vascular degeneration and inflammation as major factors in blast-induced brain injury, but the chronic neuropathological consequences remained unclear. 

Hypothesis: This study hypothesized that repetitive low-level blast exposure produces delayed vascular degeneration leading to chronic neuroinflammation, synaptic alterations and the development of vascular malformations. 

Methods: The authors exposed male rats to three 74.5-kPa blasts and examined their brains 13 months later. Vascular networks were reconstructed and quantified using micro-CT with Vesselucida 360 and Vesselucida Explorer. Histology, immunohistochemistry, electron microscopy and Western blotting assessed inflammation, vascular remodeling and synaptic proteins. 

Results: Blast-exposed rats exhibited late perivascular inflammation, apoptotic microglia and astrocytes, and vascular constriction with reduced hippocampal vessel length, diameter and volume. These regions showed neuronal loss, dendritic degeneration and degradation of vascular extracellular matrix. Synaptic proteins PSD95, spinophilin and synaptophysin were significantly decreased. Arteriovenous malformations and vascular tortuosity developed near cortical tears, indicating shear-related remodeling. 

Conclusions: Chronic blast exposure causes progressive neurovascular injury characterized by inflammation, synaptic loss and vascular malformations, implicating delayed vascular remodeling as a key mechanism in long-term blast-related neuropathology.