期刊论文详细信息
Acta Neuropathologica Communications
Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation
Rania Abutarboush1  Usmah Kawoos1  Stephen T. Ahlers1  Gregory A. Elder2  Rita De Gasperi2  Sam Gandy2  Allison Sowa3  Patrick R. Hof3  Georgina S. Perez Garcia3  William G. Janssen3  Miguel A. Gama Sosa4  David G. Cook5  Timothy Tetreault6  Susan J. Tappan6  Benjamin Ache7  Seth Hogg7  Gissel M. Perez8  Dylan Pryor8 
[1] Department of Neurotrauma, Operational and Undersea Medicine Directorate, Naval Medical Research Center;Department of Psychiatry, Icahn School of Medicine at Mount Sinai;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai;General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center;Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System;MBF Bioscience LLC;Micro Photonics, Inc;Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center;
关键词: Animal model;    Blast;    Brain;    Chronic;    Vascular;    Neurovascular unit;   
DOI  :  10.1186/s40478-021-01269-5
来源: DOAJ
【 摘 要 】

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.

【 授权许可】

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