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Repeated mild traumatic brain injury results in long-term white-matter disruption.

ABSTRACT: Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI.

SUBMITTER: Donovan V

PROVIDER: S-EPMC3982100 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Repeated mild traumatic brain injury results in long-term white-matter disruption.

Donovan Virginia V Kim Claudia C Anugerah Ariana K AK Coats Jacqueline S JS Oyoyo Udochuwku U Pardo Andrea C AC Obenaus Andre A

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20140129 4

Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to t ...[more]

PMID: 24473478

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Project description:Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function.

Dataset Information

Repeated mild traumatic brain injury results in long-term white-matter disruption.

Publications

Repeated mild traumatic brain injury results in long-term white-matter disruption.

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