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

Author:

Tweedie David1ORCID,Karnati Hanuma Kumar1,Mullins Roger2,Pick Chaim G3,Hoffer Barry J4,Goetzl Edward J5,Kapogiannis Dimitrios2,Greig Nigel H1ORCID

Affiliation:

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

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.

Funder

National Institutes of Health

Ari and Regine Aprijaskis Fund

Dr. Miriam and Sheldon G. Adelson Chair for the Biology of Addictive Diseases

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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