Late chronic local inflammation, synaptic alterations, vascular remodeling and arteriovenous malformations in the brains of male rats exposed to repetitive low-level blast overpressures

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

In the course of military operations in modern war theaters, blast exposures are associated with the development of a variety of mental health disorders associated with a post-traumatic stress disorder-related features, including anxiety, impulsivity, insomnia, suicidality, depression, and cognitive decline. Several lines of evidence indicate that acute and chronic cerebral vascular alterations are involved in the development of these blast-induced neuropsychiatric changes. In the present study, we investigated late occurring neuropathological events associated with cerebrovascular alterations in a rat model of repetitive low-level blast-exposures (3 × 74.5 kPa). The observed events included hippocampal hypoperfusion associated with late-onset inflammation, vascular extracellular matrix degeneration, synaptic structural changes and neuronal loss. We also demonstrate that arteriovenous malformations in exposed animals are a direct consequence of blast-induced tissue tears. Overall, our results further identify the cerebral vasculature as a main target for blast-induced damage and support the urgent need to develop early therapeutic approaches for the prevention of blast-induced late-onset neurovascular degenerative processes.

Original languageEnglish
Article number81
JournalActa Neuropathologica Communications
Volume11
Issue number1
DOIs
StatePublished - Dec 2023
Externally publishedYes

Keywords

  • Animal model
  • Blast
  • Brain
  • Chronic
  • Microglia
  • Neuroinflammation
  • Neurovascular unit
  • Rat
  • Synapse
  • Vascular
  • Vascular pathology

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