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Transcriptional profiling predicts behavioral performance in experimental mouse model of traumatic brain injury (TBI)

Yun Jiao, Alan Faden, Boris Sabirzhanov, Bogdan Stoica, Gregory L. Szeto and Jennie Leach
J Immunol May 1, 2020, 204 (1 Supplement) 75.17;
Yun Jiao
1University of Maryland, Baltimore County
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Alan Faden
2Department of Anatomy and Neurobiology, University of Maryland School of Medicine
3Department of Anesthesiology and Center for Shock, Trauma & Anesthesiology Research, University of Maryland School of Medicine
4University of Maryland Center to Advance Chronic Pain Research
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Boris Sabirzhanov
3Department of Anesthesiology and Center for Shock, Trauma & Anesthesiology Research, University of Maryland School of Medicine
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Bogdan Stoica
3Department of Anesthesiology and Center for Shock, Trauma & Anesthesiology Research, University of Maryland School of Medicine
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Gregory L. Szeto
5Chemical, Biochemical, Environmental Engineering, University of Maryland, Baltimore County
6Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland
7Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore
8Center for Biomedical Engineering and Technology, University of Maryland School of Medicine
9Translational Center for Age-Related Disease and Disparities, University of Maryland Baltimore County
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Jennie Leach
1University of Maryland, Baltimore County
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Abstract

Traumatic brain injury (TBI) is a prevailing cause of disability and death. There are no curative therapies or robust predictors of long-term neurodegenerative disease. Treatment is challenging due to poor understanding of the cellular responses and mechanisms underlying TBI. We linked transcriptional profiling, cytokine profiling, and behavioral scoring in experimental TBI to discover new insights into immune-mediated mechanisms of TBI. Mice received ipsilateral moderate controlled cortical impaction. Luminex analyses showed upregulation of inflammatory cytokines in injured cortex, hippocampus, and spinal cord. Neurobehavioral evaluations were performed, then hippocampi isolated at 28d post-TBI for RNAseq. Pathway analyses of upregulated genes were functionally enriched for glial activation, proliferation, and neuronal development. Genes involved in synaptic transmission, glutamate receptor signaling, and neuronal migration were downregulated. Partial least squares (PLS) regression successfully modeled the relationship between differentially expressed genes and behavioral scores (R2=0.94). A core 10-gene signature predicted TBI severity and behavioral score. PLS discriminant analysis (PLSDA) classified TBI severity. VIP scores were used to define a 20-gene signature in TBI based on high VIP score, high fold change, and contribution to biological function. A PLSDA model using only these 20 genes was cross-validated by bootstrap method (AUROC=0.93), indicating that these genes may identify the critical TBI-altered processes. Altogether, our analyses revealed TBI-related biological pathways, potential therapeutic targets, and gene signatures as biomarkers for TBI severity and behavioral outcomes.

  • Copyright © 2020 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 204, Issue 1 Supplement
1 May 2020
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Transcriptional profiling predicts behavioral performance in experimental mouse model of traumatic brain injury (TBI)
Yun Jiao, Alan Faden, Boris Sabirzhanov, Bogdan Stoica, Gregory L. Szeto, Jennie Leach
The Journal of Immunology May 1, 2020, 204 (1 Supplement) 75.17;

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Transcriptional profiling predicts behavioral performance in experimental mouse model of traumatic brain injury (TBI)
Yun Jiao, Alan Faden, Boris Sabirzhanov, Bogdan Stoica, Gregory L. Szeto, Jennie Leach
The Journal of Immunology May 1, 2020, 204 (1 Supplement) 75.17;
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Print ISSN 0022-1767        Online ISSN 1550-6606