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Acta Neuropathol Commun. 2019 Jan 9;7(1):6. doi: 10.1186/s40478-018-0647-5.

Low-level blast exposure disrupts gliovascular and neurovascular connections and induces a chronic vascular pathology in rat brain.

Author information

1
General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA. miguel.gama-sosa@mssm.edu.
2
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA. miguel.gama-sosa@mssm.edu.
3
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. miguel.gama-sosa@mssm.edu.
4
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA.
5
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
6
Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA.
7
Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA.
8
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
9
Department of Neurotrauma, Operational and Undersea Medicine Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA.
10
Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, 20914, USA.
11
Micro Photonics, Inc., 1550 Pond Road, Allentown, PA, 18104, USA.
12
MBF Bioscience, 185 Allen Brook Lane, Williston, VT, 05495, USA.
13
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
14
Mount Sinai Alzheimer's Disease Research Center and the Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
15
NFL Neurological Care Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
16
Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
17
Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA.

Abstract

Much concern exists over the role of blast-induced traumatic brain injury (TBI) in the chronic cognitive and mental health problems that develop in veterans and active duty military personnel. The brain vasculature is particularly sensitive to blast injury. The aim of this study was to characterize the evolving molecular and histologic alterations in the neurovascular unit induced by three repetitive low-energy blast exposures (3 × 74.5 kPa) in a rat model mimicking human mild TBI or subclinical blast exposure. High-resolution two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of purified brain vascular fractions from blast-exposed animals 6 weeks post-exposure showed decreased levels of vascular-associated glial fibrillary acidic protein (GFAP) and several neuronal intermediate filament proteins (α-internexin and the low, middle, and high molecular weight neurofilament subunits). Loss of these proteins suggested that blast exposure disrupts gliovascular and neurovascular interactions. Electron microscopy confirmed blast-induced effects on perivascular astrocytes including swelling and degeneration of astrocytic endfeet in the brain cortical vasculature. Because the astrocyte is a major sensor of neuronal activity and regulator of cerebral blood flow, structural disruption of gliovascular integrity within the neurovascular unit should impair cerebral autoregulation. Disrupted neurovascular connections to pial and parenchymal blood vessels might also affect brain circulation. Blast exposures also induced structural and functional alterations in the arterial smooth muscle layer. Interestingly, by 8 months after blast exposure, GFAP and neuronal intermediate filament expression had recovered to control levels in isolated brain vascular fractions. However, despite this recovery, a widespread vascular pathology was still apparent at 10 months after blast exposure histologically and on micro-computed tomography scanning. Thus, low-level blast exposure disrupts gliovascular and neurovascular connections while inducing a chronic vascular pathology.

KEYWORDS:

Animal model; Blast; Brain; Chronic; Gliovascular; Neurovascular; Rat; Vascular pathology

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