Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation

Miguel A. Gama Sosa*, Rita De Gasperi, Dylan Pryor, Georgina S. Perez Garcia, Gissel M. Perez, Rania Abutarboush, Usmah Kawoos, Seth Hogg, Benjamin Ache, William G. Janssen, Allison Sowa, Timothy Tetreault, David G. Cook, Susan J. Tappan, Sam Gandy, Patrick R. Hof, Stephen T. Ahlers, Gregory A. Elder

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Cerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with the development of an age-dependent post-traumatic stress disorder-like phenotype. To investigate the evolution of blast-induced chronic vascular degenerative changes, Long-Evans rats were blast-exposed (3 × 74.5 kPa) and their brains analyzed at different times post-exposure by X-ray microcomputed tomography, immunohistochemistry and electron microscopy. On microcomputed tomography scans, regional cerebral vascular attenuation or occlusion was observed as early as 48 h post-blast, and cerebral vascular disorganization was visible at 6 weeks and more accentuated at 13 months post-blast. Progression of the late-onset pathology was characterized by detachment of the endothelial and smooth muscle cellular elements from the neuropil due to degeneration and loss of arteriolar perivascular astrocytes. Development of this pathology was associated with vascular remodeling and neuroinflammation as increased levels of matrix metalloproteinases (MMP-2 and MMP-9), collagen type IV loss, and microglial activation were observed in the affected vasculature. Blast-induced chronic alterations within the neurovascular unit should affect cerebral blood circulation, glymphatic flow and intramural periarterial drainage, all of which may contribute to development of the blast-induced behavioral phenotype. Our results also identify astrocytic degeneration as a potential target for the development of therapies to treat blast-induced brain injury.

Original languageEnglish
Article number167
JournalActa Neuropathologica Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Animal model
  • Astrocyte
  • Blast
  • Brain
  • Chronic
  • Neurovascular unit
  • Rat
  • Tight junctions
  • Vascular
  • Vascular pathology

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