Time-dependent cytokine and chemokine changes in mouse cerebral cortex following a mild traumatic brain injury

Elife. 2020 Aug 17:9:e55827. doi: 10.7554/eLife.55827.

Abstract

Traumatic brain injury (TBI) is a serious global health problem, many individuals live with TBI-related neurological dysfunction. A lack of biomarkers of TBI has impeded medication development. To identify new potential biomarkers, we time-dependently evaluated mouse brain tissue and neuronally derived plasma extracellular vesicle proteins in a mild model of TBI with parallels to concussive head injury. Mice (CD-1, 30-40 g) received a sham procedure or 30 g weight-drop and were euthanized 8, 24, 48, 72, 96 hr, 7, 14 and 30 days later. We quantified ipsilateral cortical proteins, many of which differed from sham by 8 hours post-mTBI, particularly GAS-1 and VEGF-B were increased while CXCL16 reduced, 23 proteins changed in 4 or more of the time points. Gene ontology pathways mapped from altered proteins over time related to pathological and physiological processes. Validation of proteins identified in this study may provide utility as treatment response biomarkers.

Keywords: immunology; inflammation; mild traumatic brain injury; mouse; neuroscience; protein marker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood*
  • Brain Concussion*
  • Brain Injuries / pathology
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cerebral Cortex / pathology
  • Chemokine CXCL16 / analysis
  • Chemokine CXCL16 / genetics
  • Chemokine CXCL16 / metabolism
  • Chemokines* / analysis
  • Chemokines* / genetics
  • Chemokines* / metabolism
  • Cytokines* / analysis
  • Cytokines* / genetics
  • Cytokines* / metabolism
  • Disease Models, Animal
  • Extracellular Vesicles / metabolism
  • GPI-Linked Proteins / analysis
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Ontology
  • Gene Regulatory Networks
  • Mice
  • Transcriptome
  • Vascular Endothelial Growth Factor B / analysis
  • Vascular Endothelial Growth Factor B / genetics
  • Vascular Endothelial Growth Factor B / metabolism

Substances

  • Biomarkers
  • Cell Cycle Proteins
  • Chemokine CXCL16
  • Chemokines
  • Cxcl16 protein, mouse
  • Cytokines
  • GPI-Linked Proteins
  • Gas1 protein, mouse
  • Vascular Endothelial Growth Factor B
  • vascular endothelial growth factor B, mouse