@article{5f15630ae9b34e94bbacede2996eecdd,
title = "Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation",
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.",
keywords = "Animal model, Astrocyte, Blast, Brain, Chronic, Neurovascular unit, Rat, Tight junctions, Vascular, Vascular pathology",
author = "{Gama Sosa}, {Miguel A.} and {De Gasperi}, Rita and Dylan Pryor and {Perez Garcia}, {Georgina S.} and Perez, {Gissel M.} and Rania Abutarboush and Usmah Kawoos and Seth Hogg and Benjamin Ache and Janssen, {William G.} and Allison Sowa and Timothy Tetreault and Cook, {David G.} and Tappan, {Susan J.} and Sam Gandy and Hof, {Patrick R.} and Ahlers, {Stephen T.} and Elder, {Gregory A.}",
note = "Funding Information: We sincerely thank the anonymous reviewers whose constructive suggestions improved this manuscript considerably. We also thank Dr. Virginia Lee for generously providing the rat anti-GFAP antibody. The work described in this paper was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Awards 1I01BX0004067-01 (GE), I01RX002660-01 (GE), 1 I21 RX003459-01 (MAGS), 1 I21 RX002069-01 (MAGS) and 1 I21 RX002876-01 (MAGS); by the Department of Defense work unit number 0000B999.0000.000.A1503, the Alzheimer{\textquoteright}s Drug Discovery Foundation (SG) and by NIA P50 AG011508 and P30 AG066514 to Mary Sano (SG, PRH). MAGS, RDG, DP, GMP, GE, SG, RA, UK, DGC and STA are employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that {\textquoteleft}Copyright protection under this title is not available for any work of the United States Government.{\textquoteright} Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person{\textquoteright}s official duties. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, Department of Veterans Affairs, nor the U.S. Government. Funding Information: We sincerely thank the anonymous reviewers whose constructive suggestions improved this manuscript considerably. We also thank Dr. Virginia Lee for generously providing the rat anti-GFAP antibody. The work described in this paper was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Awards 1I01BX0004067-01 (GE), I01RX002660-01 (GE), 1 I21 RX003459-01 (MAGS), 1 I21 RX002069-01 (MAGS) and 1 I21 RX002876-01 (MAGS); by the Department of Defense work unit number 0000B999.0000.000.A1503, the Alzheimer{\textquoteright}s Drug Discovery Foundation (SG) and by NIA P50 AG011508 and P30 AG066514 to Mary Sano (SG, PRH). MAGS, RDG, DP, GMP, GE, SG, RA, UK, DGC and STA are employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that {\textquoteleft}Copyright protection under this title is not available for any work of the United States Government.{\textquoteright} Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person{\textquoteright}s official duties. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, Department of Veterans Affairs, nor the U.S. Government. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1186/s40478-021-01269-5",
language = "English",
volume = "9",
journal = "Acta neuropathologica communications",
issn = "2051-5960",
publisher = "BioMed Central Ltd.",
number = "1",
}