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The problem of axonal injury in the brains of veterans with histories of blast exposure

INTRODUCTION: Blast injury to brain, a hundred-year old problem with poorly characterized neuropathology, has resurfaced as health concern in recent deployments in Iraq and Afghanistan. To characterize the neuropathology of blast injury, we examined the brains of veterans for the presence of amyloid...

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Autores principales: Ryu, Jiwon, Horkayne-Szakaly, Iren, Xu, Leyan, Pletnikova, Olga, Leri, Francesco, Eberhart, Charles, Troncoso, Juan C, Koliatsos, Vassilis E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260204/
https://www.ncbi.nlm.nih.gov/pubmed/25422066
http://dx.doi.org/10.1186/s40478-014-0153-3
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author Ryu, Jiwon
Horkayne-Szakaly, Iren
Xu, Leyan
Pletnikova, Olga
Leri, Francesco
Eberhart, Charles
Troncoso, Juan C
Koliatsos, Vassilis E
author_facet Ryu, Jiwon
Horkayne-Szakaly, Iren
Xu, Leyan
Pletnikova, Olga
Leri, Francesco
Eberhart, Charles
Troncoso, Juan C
Koliatsos, Vassilis E
author_sort Ryu, Jiwon
collection PubMed
description INTRODUCTION: Blast injury to brain, a hundred-year old problem with poorly characterized neuropathology, has resurfaced as health concern in recent deployments in Iraq and Afghanistan. To characterize the neuropathology of blast injury, we examined the brains of veterans for the presence of amyloid precursor protein (APP)-positive axonal swellings typical of diffuse axonal injury (DAI) and compared them to healthy controls as well as controls with opiate overdose, anoxic-ischemic encephalopathy, and non-blast TBI (falls and motor vehicle crashes). RESULTS: In cases with blast history, we found APP (+) axonal abnormalities in several brain sites, especially the medial dorsal frontal white matter. In white matter, these abnormalities were featured primarily by clusters of axonal spheroids or varicosities in a honeycomb pattern with perivascular distribution. Axonal abnormalities colocalized with IBA1 (+) reactive microglia and had an appearance that was distinct from classical DAI encountered in TBI due to motor vehicle crashes. Opiate overdose cases also showed APP (+) axonal abnormalities, but the intensity of these lesions was lower compared to cases with blast histories and there was no clear association of such lesions with microglial activation. CONCLUSIONS: Our findings demonstrate that many cases with history of blast exposure are featured by APP (+) axonopathy that may be related to blast exposure, but an important role for opiate overdose, antemortem anoxia, and concurrent blunt TBI events in war theater or elsewhere cannot be discounted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-014-0153-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-42602042014-12-09 The problem of axonal injury in the brains of veterans with histories of blast exposure Ryu, Jiwon Horkayne-Szakaly, Iren Xu, Leyan Pletnikova, Olga Leri, Francesco Eberhart, Charles Troncoso, Juan C Koliatsos, Vassilis E Acta Neuropathol Commun Research INTRODUCTION: Blast injury to brain, a hundred-year old problem with poorly characterized neuropathology, has resurfaced as health concern in recent deployments in Iraq and Afghanistan. To characterize the neuropathology of blast injury, we examined the brains of veterans for the presence of amyloid precursor protein (APP)-positive axonal swellings typical of diffuse axonal injury (DAI) and compared them to healthy controls as well as controls with opiate overdose, anoxic-ischemic encephalopathy, and non-blast TBI (falls and motor vehicle crashes). RESULTS: In cases with blast history, we found APP (+) axonal abnormalities in several brain sites, especially the medial dorsal frontal white matter. In white matter, these abnormalities were featured primarily by clusters of axonal spheroids or varicosities in a honeycomb pattern with perivascular distribution. Axonal abnormalities colocalized with IBA1 (+) reactive microglia and had an appearance that was distinct from classical DAI encountered in TBI due to motor vehicle crashes. Opiate overdose cases also showed APP (+) axonal abnormalities, but the intensity of these lesions was lower compared to cases with blast histories and there was no clear association of such lesions with microglial activation. CONCLUSIONS: Our findings demonstrate that many cases with history of blast exposure are featured by APP (+) axonopathy that may be related to blast exposure, but an important role for opiate overdose, antemortem anoxia, and concurrent blunt TBI events in war theater or elsewhere cannot be discounted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-014-0153-3) contains supplementary material, which is available to authorized users. BioMed Central 2014-11-25 /pmc/articles/PMC4260204/ /pubmed/25422066 http://dx.doi.org/10.1186/s40478-014-0153-3 Text en © Ryu et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ryu, Jiwon
Horkayne-Szakaly, Iren
Xu, Leyan
Pletnikova, Olga
Leri, Francesco
Eberhart, Charles
Troncoso, Juan C
Koliatsos, Vassilis E
The problem of axonal injury in the brains of veterans with histories of blast exposure
title The problem of axonal injury in the brains of veterans with histories of blast exposure
title_full The problem of axonal injury in the brains of veterans with histories of blast exposure
title_fullStr The problem of axonal injury in the brains of veterans with histories of blast exposure
title_full_unstemmed The problem of axonal injury in the brains of veterans with histories of blast exposure
title_short The problem of axonal injury in the brains of veterans with histories of blast exposure
title_sort problem of axonal injury in the brains of veterans with histories of blast exposure
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260204/
https://www.ncbi.nlm.nih.gov/pubmed/25422066
http://dx.doi.org/10.1186/s40478-014-0153-3
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