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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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Perivascular distribution of APP-immunoreactive axon abnormalities demonstrated here on adjacent sections, one of which (top) was processed for APP immunohistochemistry and the other (bottom) with Masson trichrome stain (images taken from Case 3). Numbers indicate corresponding blood vessels. Note that axonal abnormalities encircle aniline blue (+) thick-walled vessels representing arterioles (#1, 3, 5), but not thin-walled vessels that are venules (#2, 4). (4) is not evident on top section and only its position was marked as such. Size bars: 50 μm.
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Fig3: Perivascular distribution of APP-immunoreactive axon abnormalities demonstrated here on adjacent sections, one of which (top) was processed for APP immunohistochemistry and the other (bottom) with Masson trichrome stain (images taken from Case 3). Numbers indicate corresponding blood vessels. Note that axonal abnormalities encircle aniline blue (+) thick-walled vessels representing arterioles (#1, 3, 5), but not thin-walled vessels that are venules (#2, 4). (4) is not evident on top section and only its position was marked as such. Size bars: 50 μm.

Mentions: The comparison of sections immunostained with APP and adjacent sections stained with Masson’s trichrome in regions with honeycomb pattern of axonal lesions shows that APP (+) perivascular abnormalities are associated with arterioles, but not venules (Figure 3).Figure 3


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)

Perivascular distribution of APP-immunoreactive axon abnormalities demonstrated here on adjacent sections, one of which (top) was processed for APP immunohistochemistry and the other (bottom) with Masson trichrome stain (images taken from Case 3). Numbers indicate corresponding blood vessels. Note that axonal abnormalities encircle aniline blue (+) thick-walled vessels representing arterioles (#1, 3, 5), but not thin-walled vessels that are venules (#2, 4). (4) is not evident on top section and only its position was marked as such. Size bars: 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Perivascular distribution of APP-immunoreactive axon abnormalities demonstrated here on adjacent sections, one of which (top) was processed for APP immunohistochemistry and the other (bottom) with Masson trichrome stain (images taken from Case 3). Numbers indicate corresponding blood vessels. Note that axonal abnormalities encircle aniline blue (+) thick-walled vessels representing arterioles (#1, 3, 5), but not thin-walled vessels that are venules (#2, 4). (4) is not evident on top section and only its position was marked as such. Size bars: 50 μm.
Mentions: The comparison of sections immunostained with APP and adjacent sections stained with Masson’s trichrome in regions with honeycomb pattern of axonal lesions shows that APP (+) perivascular abnormalities are associated with arterioles, but not venules (Figure 3).Figure 3

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