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

雄性大鼠大脑暴露于反复低水平冲击过压后,会出现晚期慢性局部炎症、突触改变、血管重塑和动静脉畸形

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作者: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, G

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.

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