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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

Further magnification of areas indicated with arrows in Figure6. Arrangement of panels is exactly as in Figure 6. These images illustrate in greater detail the anatomical differences of injured axons among classical traumatic DAI (a and b from Case 20, c and d from Case 21), blast (e and f from case 4, g from Case 5, h from Case 3), and opiate overdose (i and j from Case 9, k from Case 7, l from Case 6). Size bars: 20 μm.
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Fig7: Further magnification of areas indicated with arrows in Figure6. Arrangement of panels is exactly as in Figure 6. These images illustrate in greater detail the anatomical differences of injured axons among classical traumatic DAI (a and b from Case 20, c and d from Case 21), blast (e and f from case 4, g from Case 5, h from Case 3), and opiate overdose (i and j from Case 9, k from Case 7, l from Case 6). Size bars: 20 μm.

Mentions: As shown in Figures 6 and 7, the microscopic appearance of axonal abnormalities is different among cases with histories of motor vehicle crash (the classical scenario causing DAI) versus blast versus opiate overdose. In coronal sections like the ones used in this study, axonal abnormalities in cases of motor vehicle crash are thick with prominent undulations and classical axon bulbs; in the case of opiate overdose, axonal abnormalities are thin and straight, with multiple varicosities in the course of a single axon; in blast cases, axonal abnormalities fall in-between classical DAI and opiate overdose cases and feature prominent varicosities and spheroids (Figure 6 and, in further magnification, Figure 7).Figure 6


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)

Further magnification of areas indicated with arrows in Figure6. Arrangement of panels is exactly as in Figure 6. These images illustrate in greater detail the anatomical differences of injured axons among classical traumatic DAI (a and b from Case 20, c and d from Case 21), blast (e and f from case 4, g from Case 5, h from Case 3), and opiate overdose (i and j from Case 9, k from Case 7, l from Case 6). Size bars: 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig7: Further magnification of areas indicated with arrows in Figure6. Arrangement of panels is exactly as in Figure 6. These images illustrate in greater detail the anatomical differences of injured axons among classical traumatic DAI (a and b from Case 20, c and d from Case 21), blast (e and f from case 4, g from Case 5, h from Case 3), and opiate overdose (i and j from Case 9, k from Case 7, l from Case 6). Size bars: 20 μm.
Mentions: As shown in Figures 6 and 7, the microscopic appearance of axonal abnormalities is different among cases with histories of motor vehicle crash (the classical scenario causing DAI) versus blast versus opiate overdose. In coronal sections like the ones used in this study, axonal abnormalities in cases of motor vehicle crash are thick with prominent undulations and classical axon bulbs; in the case of opiate overdose, axonal abnormalities are thin and straight, with multiple varicosities in the course of a single axon; in blast cases, axonal abnormalities fall in-between classical DAI and opiate overdose cases and feature prominent varicosities and spheroids (Figure 6 and, in further magnification, Figure 7).Figure 6

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