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

David Tweedie; Hanuma Kumar Karnati; Roger Mullins; Chaim G Pick; Barry J Hoffer; Edward J Goetzl; Dimitrios Kapogiannis; Nigel H Greig

doi:10.7554/eLife.55827

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.

Authors

David Tweedie^#¹, Hanuma Kumar Karnati^#¹, Roger Mullins², Chaim G Pick³, Barry J Hoffer⁴, Edward J Goetzl⁵, Dimitrios Kapogiannis², Nigel H Greig¹

Affiliations

¹ Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, Baltimore, United States.
² Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, NIH, Baltimore, United States.
³ Department of Anatomy and Anthropology, Sackler School of Medicine, Sylvan Adams Sports Institute, and Dr. Miriam and SheldonG. Adelson Chair and Center for the Biology of Addictive Diseases, Tel Aviv University, Tel Aviv, Israel.
⁴ Department of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, United States.
⁵ Department of Medicine, University of California Medical Center, San Francisco, San Francisco, United States.

^# Contributed equally.

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding