Time-dependent cytokine and chemokine changes in mouse cerebral cortex following a mild traumatic brain injury
- National Institute on Aging, NIH, United States
- Sackler School of Medicine, Tel-Aviv University, Israel
- Case Western Reserve University, United States
- University of California Medical Center, United States
Abstract
Traumatic brain injury (TBI) is a serious global health concern, 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 vesicles 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 hours, 7, 14 and 30 days later. We quantified ipsilateral cortical proteins. Many of them differed from 8 hours onwards post mTBI compared to sham, 23 proteins changed in 4 or more of 8 different time points. Gene ontology pathways mapped from altered proteins over time related to pathological and physiological processes. Further validation of proteins identified in this study may provide utility as treatment response biomarkers.
Data availability
All data generated by US NIH funded research is available to the public, the data generated in this study is available to the public. The data used to generate the Figures in the manuscript are provided as source data files.
Article and author information
Author details
Funding
National Institutes of Health (AG000944)
- Nigel H Greig
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: AlI animal studies were conducted at the Intramural Research Program of the National Institute on Aging, Baltimore, MD, USA. Experimental animal protocols were approved by the Animal Care and Use Committee of the Intramural Research Program, National Institute on Aging (438-TGB-2022) and were in compliance with the guidelines for animal experimentation of the National Research Council (Committee for the Update of the Guide for the Care and Use of Laboratory Animals, 2011) and the National Institutes of Health (DHEW publication 85-23, revised, 1995).
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 2,767
- views
-
- 355
- downloads
-
- 28
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Time-dependent cytokine and chemokine changes in mouse cerebral cortex following a mild traumatic brain injury
eLife 9:e55827.
https://doi.org/10.7554/eLife.55827
Further reading
-
- Immunology and Inflammation
Macrophages control intracellular pathogens like Salmonella by using two caspase enzymes at different times during infection.
-
- Immunology and Inflammation
- Microbiology and Infectious Disease
The members of the Mycobacterium tuberculosis complex (MTBC) causing human tuberculosis comprise 10 phylogenetic lineages that differ in their geographical distribution. The human consequences of this phylogenetic diversity remain poorly understood. Here, we assessed the phenotypic properties at the host-pathogen interface of 14 clinical strains representing five major MTBC lineages. Using a human in vitro granuloma model combined with bacterial load assessment, microscopy, flow cytometry, and multiplexed-bead arrays, we observed considerable intra-lineage diversity. Yet, modern lineages were overall associated with increased growth rate and more pronounced granulomatous responses. MTBC lineages exhibited distinct propensities to accumulate triglyceride lipid droplets—a phenotype associated with dormancy—that was particularly pronounced in lineage 2 and reduced in lineage 3 strains. The most favorable granuloma responses were associated with strong CD4 and CD8 T cell activation as well as inflammatory responses mediated by CXCL9, granzyme B, and TNF. Both of which showed consistent negative correlation with bacterial proliferation across genetically distant MTBC strains of different lineages. Taken together, our data indicate that different virulence strategies and protective immune traits associate with MTBC genetic diversity at lineage and strain level.
