4.8 Article

Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury

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SCIENCE TRANSLATIONAL MEDICINE
卷 13, 期 613, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.abg9922

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资金

  1. ERA-NET NEURON Cofund, European Research Projects on External Insults to the Nervous System call, within the Horizon 2020 [MR/R004528/1]
  2. Alzheimer's Research UK Clinical Research Fellowship
  3. U.K. Dementia Research Institute (DRI) Care Research and Technology Centre
  4. National Institute of Health Research (NIHR) Professorship [NIHR-RP-011-048]
  5. NIHR Clinical Research Facility and Biomedical Research Centre (BRC) at Imperial College Healthcare NHS Trust
  6. Medical Research Council Clinician Scientist Fellowship
  7. Wallenberg Scholarship
  8. Swedish Research Council [2018-02532]
  9. European Research Council [681712]
  10. Swedish State Support for Clinical Research [ALFGBG-720931]
  11. Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862]
  12. European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant [860197]
  13. U.K. Dementia Research Institute at UCL
  14. Swiss National Science Foundation [31NE30_173675, 32003B_188501]
  15. Swiss National Science Foundation (SNF) [32003B_188501, 31NE30_173675] Funding Source: Swiss National Science Foundation (SNF)

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Plasma NfL serves as a sensitive and clinically meaningful measure of axonal injury resulting from TBI, validated through advanced MRI, cerebral microdialysis, and experimental models. The results support the incorporation of NfL sampling into clinical practice to aid in diagnosis and improve prognosis.
Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.

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