Defining an Analytic Framework to Evaluate Quantitative MRI Markers of Traumatic Axonal Injury: Preliminary Results in a Mouse Closed Head Injury Model

Haber, Margalit; Hutchinson, Elizabeth; Sadeghi, Neda; Cheng, Wai Hang; Namjoshi, Dhananjay; Cripton, Peter A.; İrfanoğlu, M. Okan; Wellington, Cheryl L.; Pierpaoli, Carlo

doi:10.1523/eneuro.0164-17.2017

Cited by 34 publications

(42 citation statements)

References 45 publications

(46 reference statements)

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“…In our present long-term TBI study, the axonal injury marker, APP, is not detectable in the brain 24 weeks after TBI, suggesting that the fast axonal transport accumulation of APP may occur only in the acute phase, but not in the late subacute phase of TBI. This view is in line with the findings from other studies showing that APP is upregulated at 1d after TBI, and turns to sparsely expressed at 7d after TBI in mice [63][64][65][66]. In humans, APP accumulation is seen within hours after TBI [67].…”

Section: Discussionsupporting

confidence: 91%

The Contribution of Stem Cell Factor and Granulocyte Colony-Stimulating Factor in Reducing Neurodegeneration and Promoting Neural Network Reorganization after Traumatic Brain Injury

Russell

Qiu

et al. 2020

Preprint

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Background Traumatic brain injury (TBI) is a major cause of death and disability in young adults worldwide. TBI-induced long-term cognitive deficits represent a growing clinical problem. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are involved in neuroprotection and neuronal plasticity. However, the knowledge concerning reparative efficacy of SCF+G-CSF treatment in post-acute TBI recovery remains incomplete. This study aims to determine the efficacy of SCF+G-CSF on post-acute TBI recovery in young adult mice. The controlled cortical impact model of TBI was used for inducing a severe damage in the motor cortex of the right hemisphere in 8-week-old male C57BL mice. SCF+G-CSF treatment was initiated 3 weeks after induction of TBI. Results Severe TBI led to persistent motor functional deficits (Rota-Rod test) and impaired spatial learning and memory (Morris water maze test). SCF+G-CSF treatment significantly improved the severe TBI-impaired spatial learning and memory 6 weeks after treatment. TBI also caused significant increases of Fluoro-Jade C positive degenerating neurons in bilateral frontal cortex, striatum and hippocampus, and significant reductions in MAP2 + apical dendrites and overgrowth of SMI312 + axons in peri-TBI cavity frontal cortex and in the ipsilateral hippocampal CA1 at 24 weeks post-TBI. SCF+G-CSF treatment significantly reduced TBI-induced neurodegeneration in the contralateral frontal cortex and hippocampal CA1, increased MAP2 + apical dendrites in the peri-TBI cavity frontal cortex, and prevented TBI-induced axonal overgrowth in both the peri-TBI cavity frontal cortex and ipsilateral hippocampal CA1. Conclusions These findings reveal a novel pathology of axonal overgrowth after TBI and demonstrate a therapeutic potential of SCF+G-CSF in ameliorating TBI-induced long-term neuronal pathology, neural network malformation, and impairments in spatial learning and memory.

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Section: Discussionsupporting

confidence: 91%

The Contribution of Stem Cell Factor and Granulocyte Colony-Stimulating Factor in Reducing Neurodegeneration and Promoting Neural Network Reorganization after Traumatic Brain Injury

Russell

Qiu

et al. 2020

Preprint

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“…Similar to our findings, a model of Wallerian degeneration following dorsal root axotomy in the rat revealed reduced parallel diffusivity in vivo within the ipsilateral dorsal column correlating with loss of a phosphorylated heavy chain neurofilament (NF-H), over a span of 3 to 30 days after injury. 20 In an animal model of repetitive rotational head acceleration, patterns of white matter tract damage identified by reduced fractional anisotropy were comparable to white matter injury identified by increased silver staining; 21 likewise, silver staining reflected relative anisotropy in the corpus callosum in another mild repetitive closed head injury model. 22 In human tissue, a correlation was identified between fractional anisotropy and axonal disruption as measured by the power coherence of myelin black gold staining at a resolution of 250 x 250 x 500 µm 3 in cases of chronic traumatic encephalopathy.…”

Section: Discussionmentioning

confidence: 87%

Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study

Nolan

Petersen²,

Iacono

et al. 2020

Preprint

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Diffusion tractography MRI can infer changes in network connectivity in patients with traumatic brain injury (TBI), but pathological substrates of disconnected tracts have not been well-defined due to a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750 μm resolution, followed by histopathologic evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein and loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.

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“…Next, we needed to confirm that we are able to detect the injury effect and replicate the findings from Haber et al (2017).…”

Section: Discussionmentioning

confidence: 98%

“…A specific ROI encompassing the optic tract and brachium of the superior colliculus was used for this analysis. This ROI was defined because these two regions had been shown to be the most severely injured in CHIMERA in a previous ex vivo study (Haber et al, 2017).…”

Section: Optic Tract and Brachium Region Of Interest (Roi)mentioning

confidence: 99%

Investigation of the effect of dietary intake of omega‐3 polyunsaturated fatty acids on trauma‐induced white matter injury with quantitative diffusion MRI in mice

Reyes

Haight

Desai

et al. 2020

J of Neuroscience Research

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Defining an Analytic Framework to Evaluate Quantitative MRI Markers of Traumatic Axonal Injury: Preliminary Results in a Mouse Closed Head Injury Model

Abstract: Visual Abstract

Cited by 34 publications

References 45 publications

The Contribution of Stem Cell Factor and Granulocyte Colony-Stimulating Factor in Reducing Neurodegeneration and Promoting Neural Network Reorganization after Traumatic Brain Injury

The Contribution of Stem Cell Factor and Granulocyte Colony-Stimulating Factor in Reducing Neurodegeneration and Promoting Neural Network Reorganization after Traumatic Brain Injury

Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study

Investigation of the effect of dietary intake of omega‐3 polyunsaturated fatty acids on trauma‐induced white matter injury with quantitative diffusion MRI in mice

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