Gene Expression Alterations in Peripheral Blood Following Sport-Related Concussion in a Prospective Cohort of Collegiate Athletes: A Concussion Assessment, Research and Education (CARE) Consortium Study.

Journal

Sports medicine (Auckland, N.Z.)
ISSN: 1179-2035
Titre abrégé: Sports Med
Pays: New Zealand
ID NLM: 8412297

Informations de publication

Date de publication:
08 Nov 2023
Historique:
accepted: 08 10 2023
medline: 8 11 2023
pubmed: 8 11 2023
entrez: 8 11 2023
Statut: aheadofprint

Résumé

Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury. The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery. We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline. Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion. Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.

Sections du résumé

BACKGROUND BACKGROUND
Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury.
OBJECTIVE OBJECTIVE
The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery.
METHODS METHODS
We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline.
RESULTS RESULTS
Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion.
CONCLUSIONS CONCLUSIONS
Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.

Identifiants

DOI: 10.1007/s40279-023-01951-9 PMID: 37938533
pubmed: 37938533
doi: 10.1007/s40279-023-01951-9
pii: 10.1007/s40279-023-01951-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NCATS NIH HHS
ID : UL1TR002529
Pays : United States
Organisme : NCRR NIH HHS
ID : RR020128
Pays : United States

Investigateurs

Darren Campbell (D)
Jonathan Jackson (J)
Megan Houston (M)
Christopher Giza (C)
Joshua Goldman (J)
Kevin Guskiewicz (K)
Jason P Mihalik (JP)

Informations de copyright

© 2023. The Author(s).

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Auteurs

Edward Simpson (E)

Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN, USA.
ORCID: 0000-0001-9015-9864

Jill L Reiter (JL)

Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 W 10 St, Suite 5000, Indianapolis, IN, 46202, USA.
ORCID: 0000-0001-5460-2355

Jie Ren (J)

Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
ORCID: 0000-0002-7823-6262

Zhiqi Zhang (Z)

Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
ORCID: 0009-0001-7214-1959

Kelly N Nudelman (KN)

Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 W 10 St, Suite 5000, Indianapolis, IN, 46202, USA.
ORCID: 0000-0003-4040-1717

Larry D Riggen (LD)

Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.

Michael D Menser (MD)

Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
ORCID: 0009-0007-4536-1925

Jaroslaw Harezlak (J)

Department of Epidemiology and Biostatistics, Indiana University School of Public Health, Bloomington, IN, USA.
ORCID: 0000-0002-3070-7686

Tatiana M Foroud (TM)

Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 W 10 St, Suite 5000, Indianapolis, IN, 46202, USA.
ORCID: 0000-0002-5549-2212

Andrew J Saykin (AJ)

Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 W 10 St, Suite 5000, Indianapolis, IN, 46202, USA.
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
ORCID: 0000-0002-1376-8532

Alison Brooks (A)

Department of Orthopedics, University of Wisconsin, Madison, WI, USA.

Kenneth L Cameron (KL)

Department of Orthopaedic Surgery, Keller Army Community Hospital, United States Military Academy, West Point, NY, USA.
Department of Physical Medicine and Rehabilitation, Uniformed Services University, Bethesda, MD, USA.

Stefan M Duma (SM)

Institute for Critical Technology and Applied Science, Virginia Tech, Blacksburg, VA, USA.

Gerald McGinty (G)

United States Air Force Academy, Colorado Springs, CO, 80840, USA.

Steven Rowson (S)

Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, USA.

Steven J Svoboda (SJ)

Department of Orthopaedic Surgery, Keller Army Community Hospital, United States Military Academy, West Point, NY, USA.

Steven P Broglio (SP)

Michigan Concussion Center, University of Michigan, Ann Arbor, MI, USA.
ORCID: 0000-0002-2282-9325

Michael A McCrea (MA)

Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA.

Paul F Pasquina (PF)

Physical Medicine and Rehabilitation Training, Walter Reed Army Medical Center, Washington, DC, USA.

Thomas W McAllister (TW)

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.

Yunlong Liu (Y)

Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN, USA. yunliu@iu.edu.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 W 10 St, Suite 5000, Indianapolis, IN, 46202, USA. yunliu@iu.edu.
ORCID: 0000-0002-2699-626X

Classifications MeSH