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

Ryu J, Horkayne-Szakaly I, Xu L, Pletnikova O, Leri F, Eberhart C, Troncoso JC, Koliatsos VE - Acta Neuropathol Commun (2014)

Bottom Line: In cases with blast history, we found APP (+) axonal abnormalities in several brain sites, especially the medial dorsal frontal white matter.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. jryu4@jhmi.edu.

ABSTRACT

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.

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Related in: MedlinePlus

The typical honeycomb pattern of APP(+)staining in the superior frontal gyrus of an index case with a history of blast injury (Case 3, Table 1). (b) and (c) are enlargements of the blocked areas in (a) and (b), respectively. This case had blast exposure 1 year before death and a concussion from assault 2 months prior to death. Note the groups of tens-hundreds of axonal spheroids in the deep white matter of frontal lobe.
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Fig1: The typical honeycomb pattern of APP(+)staining in the superior frontal gyrus of an index case with a history of blast injury (Case 3, Table 1). (b) and (c) are enlargements of the blocked areas in (a) and (b), respectively. This case had blast exposure 1 year before death and a concussion from assault 2 months prior to death. Note the groups of tens-hundreds of axonal spheroids in the deep white matter of frontal lobe.

Mentions: In all cases with history of blast exposure except one (Case 2), the most consistent finding was APP-immunoreactive axonal varicosities or spheroids in the medial (parasagittal) frontal white matter, primarily in the superior and middle frontal and cingulate gyri (Figure 1). These lesions clustered in circular or semi-circular formations at short distances (50-200 μm) from blood vessels and frequently coalesced in irregularly shaped lattices forming honeycomb patterns (Figure 1a-b). Similar patterns were often seen in the white matter of the anterior and middle temporal lobe. No parietal lobe tissues were available for review. The one case with blast history that did not show APP (+) axonal abnormalities in medial frontal white matter or elsewhere in the brain (Case 2) had a history of exposure to multiple IEDs and died from gunshot wound to the head (Table 1).Figure 1


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

Ryu J, Horkayne-Szakaly I, Xu L, Pletnikova O, Leri F, Eberhart C, Troncoso JC, Koliatsos VE - Acta Neuropathol Commun (2014)

The typical honeycomb pattern of APP(+)staining in the superior frontal gyrus of an index case with a history of blast injury (Case 3, Table 1). (b) and (c) are enlargements of the blocked areas in (a) and (b), respectively. This case had blast exposure 1 year before death and a concussion from assault 2 months prior to death. Note the groups of tens-hundreds of axonal spheroids in the deep white matter of frontal lobe.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4260204&req=5

Fig1: The typical honeycomb pattern of APP(+)staining in the superior frontal gyrus of an index case with a history of blast injury (Case 3, Table 1). (b) and (c) are enlargements of the blocked areas in (a) and (b), respectively. This case had blast exposure 1 year before death and a concussion from assault 2 months prior to death. Note the groups of tens-hundreds of axonal spheroids in the deep white matter of frontal lobe.
Mentions: In all cases with history of blast exposure except one (Case 2), the most consistent finding was APP-immunoreactive axonal varicosities or spheroids in the medial (parasagittal) frontal white matter, primarily in the superior and middle frontal and cingulate gyri (Figure 1). These lesions clustered in circular or semi-circular formations at short distances (50-200 μm) from blood vessels and frequently coalesced in irregularly shaped lattices forming honeycomb patterns (Figure 1a-b). Similar patterns were often seen in the white matter of the anterior and middle temporal lobe. No parietal lobe tissues were available for review. The one case with blast history that did not show APP (+) axonal abnormalities in medial frontal white matter or elsewhere in the brain (Case 2) had a history of exposure to multiple IEDs and died from gunshot wound to the head (Table 1).Figure 1

Bottom Line: In cases with blast history, we found APP (+) axonal abnormalities in several brain sites, especially the medial dorsal frontal white matter.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. jryu4@jhmi.edu.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus