Diffuse axonal injury predicts neurodegeneration after moderate–severe traumatic brain injury

作者：Neil Graham, Amy Jolly, Karl Zimmerman, Niall Bourke, Gregory Scott, James H. Cole, Jonathan M. Schott, David Sharp · 发表于：Brain · 年份：2020 · DOI：10.1093/brain/awaa316 · 被引用次数：166 · 研究领域：Advanced Neuroimaging Techniques and Applications、Traumatic Brain Injury Research、Traumatic Brain Injury and Neurovascular Disturbances

Traumatic brain injury is associated with elevated rates of neurodegenerative diseases such as Alzheimer's disease and chronic traumatic encephalopathy. In experimental models, diffuse axonal injury triggers post-traumatic neurodegeneration, with axonal damage leading to Wallerian degeneration and toxic proteinopathies of amyloid and hyperphosphorylated tau. However, in humans the link between diffuse axonal injury and subsequent neurodegeneration has yet to be established. Here we test the hypothesis that the severity and location of diffuse axonal injury predicts the degree of progressive post-traumatic neurodegeneration. We investigated longitudinal changes in 55 patients in the chronic phase after moderate-severe traumatic brain injury and 19 healthy control subjects. Fractional anisotropy was calculated from diffusion tensor imaging as a measure of diffuse axonal injury. Jacobian determinant atrophy rates were calculated from serial volumetric T1 scans as a measure of measure post-traumatic neurodegeneration. We explored a range of potential predictors of longitudinal post-traumatic neurodegeneration and compared the variance in brain atrophy that they explained. Patients showed widespread evidence of diffuse axonal injury, with reductions of fractional anisotropy at baseline and follow-up in large parts of the white matter. No significant changes in fractional anisotropy over time were observed. In contrast, abnormally high rates of brain atrophy were seen in both the g...