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 Neuropathologica Communications

Research

Stephen T. Ahlers¹  Rania Abutarboush²  Usmah Kawoos²  Gregory A. Elder³  Rita De Gasperi⁴  Carolyn W. Zhu⁵  Merina Varghese⁶  William G. M. Janssen⁶  Allison Sowa⁶  Patrick R. Hof⁷  Georgina S. Perez Garcia⁸  Miguel A. Gama Sosa⁹  David G. Cook^1,10  Timothy Tetreault^1,11  Susan J. Tappan^1,11  Benjamin Ache^1,12  Seth Hogg^1,12  Gissel M. Perez^1,13  Dylan Pryor^1,13 

[1] Department of Neurotrauma, Operational and Undersea Medicine Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, 20910, Silver Spring, MD, USA;Department of Neurotrauma, Operational and Undersea Medicine Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, 20910, Silver Spring, MD, USA;The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Mount Sinai Alzheimer’s Disease Research Center and the Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Mount Sinai Alzheimer’s Disease Research Center and the Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Mount Sinai Alzheimer’s Disease Research Center and the Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 10029, New York, NY, USA;Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, 1660 S Columbian Way, 98108, Seattle, WA, USA;Department of Medicine, University of Washington, 1959 NE Pacific St, 98195, Seattle, WA, USA;MBF Bioscience LLC, 185 Allen Brook Lane, 05495, Williston, VT, USA;Micro Photonics, Inc, 1550 Pond Road, Suite 110, 18104, Allentown, PA, USA;Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;

关键词: Animal model;    Blast;    Brain;    Chronic;    Vascular;    Neurovascular unit;    Rat;    Vascular pathology;    Microglia;    Synapse;    Neuroinflammation;   

DOI  :  10.1186/s40478-023-01553-6

 received in 2023-03-14, accepted in 2023-03-16,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

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