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

Donald, Christine L. Mac; Dikranian, Krikor; Song, Sheng‐Kwei; Bayly, Philip V.; Holtzman, David M.; Brody, David L.

doi:10.1016/j.expneurol.2007.01.035

Cited by 275 publications

(235 citation statements)

References 85 publications

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“…For example, DTI and other advanced neuroimaging techniques can elucidate signal changes in the white matter that have been shown to correlate with axonal pathology in animal models. [106][107][108][109][110] In humans with mild TBI, DTI has also shown changes in the white matter, including both increases and decreases in fractional anisotropy and other DTI-related metrics that evolve over time. [111][112][113][114][115][116][117] In some cases, these imaging changes have been linked to varying degrees of morbidity, suggesting a causal relationship.…”

Section: Advanced Neuroimagingmentioning

confidence: 99%

Therapy Development for Diffuse Axonal Injury

Smith

Hicks

Povlishock

2013

Journal of Neurotrauma

172

146

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Diffuse axonal injury (DAI) remains a prominent feature of human traumatic brain injury (TBI) and a major player in its subsequent morbidity. The importance of this widespread axonal damage has been confirmed by multiple approaches including routine postmortem neuropathology as well as advanced imaging, which is now capable of detecting the signatures of traumatically induced axonal injury across a spectrum of traumatically brain-injured persons. Despite the increased interest in DAI and its overall implications for brain-injured patients, many questions remain about this component of TBI and its potential therapeutic targeting. To address these deficiencies and to identify future directions needed to fill critical gaps in our understanding of this component of TBI, the National Institute of Neurological Disorders and Stroke hosted a workshop in May 2011. This workshop sought to determine what is known regarding the pathogenesis of DAI in animal models of injury as well as in the human clinical setting. The workshop also addressed new tools to aid in the identification of this axonal injury while also identifying more rational therapeutic targets linked to DAI for continued preclinical investigation and, ultimately, clinical translation. This report encapsulates the oral and written components of this workshop addressing key features regarding the pathobiology of DAI, the biomechanics implicated in its initiating pathology, and those experimental animal modeling considerations that bear relevance to the biomechanical features of human TBI. Parallel considerations of alternate forms of DAI detection including, but not limited to, advanced neuroimaging, electrophysiological, biomarker, and neurobehavioral evaluations are included, together with recommendations for how these technologies can be better used and integrated for a more comprehensive appreciation of the pathobiology of DAI and its overall structural and functional implications. Lastly, the document closes with a thorough review of the targets linked to the pathogenesis of DAI, while also presenting a detailed report of those target-based therapies that have been used, to date, with a consideration of their overall implications for future preclinical discovery and subsequent translation to the clinic. Although all participants realize that various research gaps remained in our understanding and treatment of this complex component of TBI, this workshop refines these issues providing, for the first time, a comprehensive appreciation of what has been done and what critical needs remain unfulfilled.

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Section: Advanced Neuroimagingmentioning

confidence: 99%

Therapy Development for Diffuse Axonal Injury

Smith

Hicks

Povlishock

2013

Journal of Neurotrauma

172

146

View full text Add to dashboard Cite

show abstract

“…Recent experimental data indicate that white matter abnormalities detected using DTI correlate closely with neuropathological evidence of diffuse axonal injury. 28,29 In a prospective study, Sidaros et al evaluated 30 patients with severe TBI at 8 weeks and 12 months after injury. They found that decreased regional FA at 8 weeks was predictive of unfavorable outcome at 12 months.…”

Section: Critical Care Medicinementioning

confidence: 99%

Assessment of White Matter Injury and Outcome in Severe Brain Trauma. A Prospective Multicenter Cohort

Galanaud¹,

Perlbarg²,

Gupta³

et al. 2013

Survey of Anesthesiology

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“…The optical fractionator technique was used to count a systematic random sample of positively-stained axonal varicosities over the entire rostral to caudal extent of the region of interest. Details of these stereological methods have been previously described (Mac Donald et al, 2007a,2007bShitaka et al, 2011;Tran et al, 2011). In brief, for quantification of APP-stained axonal varicosities and Iba1-stained microglia, the region of the corpus callosum and external capsule from each coronal slice was outlined at low power (4 · ), followed by systematic counts of objects of interest at high power (60 · , oil immersion), of sites within the counting region randomly chosen by the StereoInvestigator software.…”

Section: Stereological Quantificationmentioning

confidence: 99%

Administration of COG1410 Reduces Axonal Amyloid Precursor Protein Immunoreactivity and Microglial Activation after Controlled Cortical Impact in Mice

Jiang

Brody

2012

Journal of Neurotrauma

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Traumatic axonal injury (TAI) accounts for at least 35% of the morbidity and mortality in traumatic brain injury (TBI) patients without space-occupying lesions. It is also believed to be a key determinant of adverse outcomes such as cognitive dysfunction across the spectrum of TBI severity. Previous studies have shown that COG1410, a synthetic peptide derived from the apolipoprotein E (apoE) receptor binding region, has anti-inflammatory effects after experimental TBI, with improvements in cognitive recovery. However, the effects of COG1410 on axonal injury following TBI are not known. The current study evaluated the effects of 1 mg/kg daily COG1410 versus saline administered intravenously starting 30 min after controlled cortical impact (CCI) injury on pericontusional TAI in young, wild-type C57BL6/J male mice. We found that COG1410 did not affect the number of amyloid precursor protein (APP)-immunoreactive axonal varicosities in the pericontusional corpus callosum and external capsule at 24 h, but reduced APP-immunoreactive varicosities by 31% at 3 days ( p = 0.0023), and 36% at 7 days ( p = 0.0009). COG1410 significantly reduced the number of Iba1-positive cells with activated microglial morphology at all three time points by 21-30%. There was no effect of COG1410 on pericontusional white matter volume or silver staining at any time point. This indicates a possible effect of COG1410 on delayed but not immediate TAI. Future studies are needed to investigate the underlying mechanisms, therapeutic time window, and physiological implications of this effect.

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

Cited by 275 publications

References 85 publications

Therapy Development for Diffuse Axonal Injury

Therapy Development for Diffuse Axonal Injury

Assessment of White Matter Injury and Outcome in Severe Brain Trauma. A Prospective Multicenter Cohort

Administration of COG1410 Reduces Axonal Amyloid Precursor Protein Immunoreactivity and Microglial Activation after Controlled Cortical Impact in Mice

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