Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Hope Center for Neurological Disorders, Washington University in St. Louis, San Luis, Missouri, United States
Experimental Neurology (Impact Factor: 4.62). 06/2007; 205(1):116-31. DOI: 10.1016/j.expneurol.2007.01.035
Source: PubMed

ABSTRACT Traumatic axonal injury (TAI) is thought to be a major contributor to cognitive dysfunction following traumatic brain injury (TBI), however TAI is difficult to diagnose or characterize non-invasively. Diffusion tensor imaging (DTI) has shown promise in detecting TAI, but direct comparison to histologically-confirmed axonal injury has not been performed. In the current study, mice were imaged with DTI, subjected to a moderate cortical controlled impact injury, and re-imaged 4-6 h and 24 h post-injury. Axonal injury was detected by amyloid beta precursor protein (APP) and neurofilament immunohistochemistry in pericontusional white matter tracts. The severity of axonal injury was quantified using stereological methods from APP stained histological sections. Two DTI parameters--axial diffusivity and relative anisotropy--were significantly reduced in the injured, pericontusional corpus callosum and external capsule, while no significant changes were seen with conventional MRI in these regions. The contusion was easily detectable on all MRI sequences. Significant correlations were found between changes in relative anisotropy and the density of APP stained axons across mice and across subregions spanning the spatial gradient of injury. The predictive value of DTI was tested using a region with DTI changes (hippocampal commissure) and a region without DTI changes (anterior commissure). Consistent with DTI predictions, there was histological detection of axonal injury in the hippocampal commissure and none in the anterior commissure. These results demonstrate that DTI is able to detect axonal injury, and support the hypothesis that DTI may be more sensitive than conventional imaging methods for this purpose.

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Available from: Krikor Dikranian, Aug 14, 2015
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    • "Chronic tissue alterations appear in the posterior part of the brain . A spatial gradient in the white matter ( Mac Donald et al . , 2007a ) , and the effect of the severity of the injury ( Rutgers et al . , 2008 ; Hylin et al . , 2013 ) or position of the impact ( Flygt et al . , 2013 ) were previously investigated . Most studies using LFP injury focus on the acute and / or subacute phases , from a few hours to several days / weeks after injury ( Graham et al . , 2000 ; F"
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    ABSTRACT: Traumatic brain injury (TBI) is a major cause of disability and death in people of all ages worldwide. An initial brain injury caused by external mechanical forces triggers a cascade of tissue changes that lead to a wide spectrum of symptoms and disabilities, such as cognitive deficits, mood or anxiety disorders, motor impairments, chronic pain, and epilepsy. We investigated the detectability of secondary injury at a chronic time-point using ex vivo diffusion tensor imaging (DTI) in a rat model of TBI, lateral fluid percussion (LFP) injury. Our analysis of ex vivo DTI data revealed persistent microstructural tissue changes in white matter tracts, such as the splenium of the corpus callosum, angular bundle, and internal capsule. Histologic examination revealed mainly loss of myelinated axons and/or iron accumulation. Gray matter areas in the thalamus exhibited an increase in fractional anisotropy associated with neurodegeneration, myelinated fiber loss, and/or calcifications at the chronic phase. In addition, we examined whether these changes could also be detected with in vivo settings at the same chronic time-point. Our results provide insight into DTI detection of microstructural changes in the chronic phase of TBI, and elucidate how these changes correlate with cellular level alterations.
    Frontiers in Neuroscience 04/2015; 9:128. DOI:10.3389/fnins.2015.00128 · 3.70 Impact Factor
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    • "ative correlation between relative anisotropy ( RA ) ( similar to FA ) to the density of beta - APP immunohistochemical staining at the acute stage ( within 24 h after injury ) ( Mac Donald et al . , 2007b ) . This suggests that axonal disruption and breakdown of axonal cytoskeleton structure are the major pathology of TAI at the acute stage ( Mac Donald et al . , 2007b ) . Over 4 weeks after injury , the RA remains decreased with axial diffusivity " pseudo - normalized " and radial diffusivity increased , confirmed by histology of demyelination , edema , neurofilament compac - tion as well as axonal disruption ( Mac Donald et al . , 2007a ) ."
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    ABSTRACT: An improved understanding and characterization of glial activation and its relationship with white matter injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination after brain trauma. Traumatic brain injury (TBI) is a significant public healthcare burden and a leading cause of death and disability in the United States. Particularly, traumatic white matter (WM) injury or traumatic axonal injury has been reported as being associated with patients' poor outcomes. However, there is very limited data reporting the importance of glial activation after TBI and its interaction with WM injury. This article presents a systematic review of traumatic WM injury and the associated glial activation, from basic science to clinical diagnosis and prognosis, from advanced neuroimaging perspective. It concludes that there is a disconnection between WM injury research and the essential role of glia which serve to restore a healthy environment for axonal regeneration following WM injury. Particularly, there is a significant lack of non-invasive means to characterize the complex pathophysiology of WM injury and glial activation in both animal models and in humans. An improved understanding and characterization of the relationship between glia and WM injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination. GLIA 2014
    Glia 11/2014; 62(11). DOI:10.1002/glia.22690 · 6.03 Impact Factor
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    • " major consequences of TBI are cognition and memory deficits which could reflect the damage to brain areas specific to those functions . However , these abnormalities may not be associated with tissue lesions or brain cell death and are often beyond detection by the standard neuronal imaging and histological methods ( but see recent reports by Mac Donald et al . , 2007 ; Bennett et al . , 2012 ) . Disruption of the integration of sensory input can have long - lasting cognitive impairment , which can occur without prior motor deficit or even after motor function has recovered ( Gagnon et al . , 1998 ; Narayan et al . , 2002 ; Draper and Ponsford , 2008 ; Faul et al . , 2010 ; Risdall and Menon , 2011 )"
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