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Salivary miRNA Expression in Children With Persistent Post-concussive Symptoms

Authors
  • Miller, Katherine E.1
  • MacDonald, James P.2, 3
  • Sullivan, Lindsay4, 5
  • Venkata, Lakshmi Prakruthi Rao1
  • Shi, Junxin6
  • Yeates, Keith Owen7
  • Chen, Su8
  • Alshaikh, Enas4
  • Taylor, H. Gerry3, 9
  • Hautmann, Amanda4
  • Asa, Nicole4, 10
  • Cohen, Daniel M.3, 11
  • Pommering, Thomas L.2, 3
  • Mardis, Elaine R.1, 3, 12
  • Yang, Jingzhen3, 4
  • 1 The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH , (United States)
  • 2 Division of Sports Medicine, Nationwide Children's Hospital, Columbus, OH , (United States)
  • 3 Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH , (United States)
  • 4 Center for Injury Research and Policy, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH , (United States)
  • 5 Discipline of Children's Studies, School of Education, National University of Ireland, Galway , (Ireland)
  • 6 Biostatistics Resource Core at Nationwide Children's Hospital, Columbus, OH , (United States)
  • 7 Department of Psychology, Alberta Children's Hospital Research Institute, and Hotchkiss Brain Institute, University of Calgary, Calgary, AB , (Canada)
  • 8 Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE , (United States)
  • 9 Biobehavioral Health Center, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH , (United States)
  • 10 Department of Epidemiology, University of Washington, Seattle, WA , (United States)
  • 11 Division of Emergency Medicine, Nationwide Children's Hospital, Columbus, OH , (United States)
  • 12 Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH , (United States)
Type
Published Article
Journal
Frontiers in Public Health
Publisher
Frontiers Media SA
Publication Date
May 30, 2022
Volume
10
Identifiers
DOI: 10.3389/fpubh.2022.890420
Source
Frontiers
Keywords
Disciplines
  • Public Health
  • Original Research
License
Green

Abstract

Background Up to one-third of concussed children develop persistent post-concussive symptoms (PPCS). The identification of biomarkers such as salivary miRNAs that detect concussed children at increased risk of PPCS has received growing attention in recent years. However, whether and how salivary miRNA expression levels differ over time between concussed children with and without PPCS is unknown. Aim To identify salivary MicroRNAs (miRNAs) whose expression levels differ over time post-concussion in children with vs. without PPCS. Methods We conducted a prospective cohort study with saliva collection at up to three timepoints: (1) within one week of injury; (2) one to two weeks post-injury; and (3) 4-weeks post-injury. Participants were children (ages 11 to 17 years) with a physician-diagnosed concussion from a single hospital center. We collected participants' daily post-concussion symptom ratings throughout their enrollment using the Post-concussion Symptom Scale, and defined PPCS as a total symptom score of ≥ 5 at 28 days post-concussion. We extracted salivary RNA from the saliva samples and measured expression levels of 827 salivary miRNAs. We then compared the longitudinal expression levels of salivary miRNAs in children with vs. without PPCS using linear models with repeated measures. Results A total of 135 saliva samples were collected from 60 children. Of the 827 miRNAs analyzed, 91 had expression levels above the calculated background threshold and were included in the differential gene expression analyses. Of these 91 miRNAs, 13 had expression levels that differed significantly across the three timepoints post-concussion between children with and without PPCS (i.e., hsa-miR-95-3p, hsa-miR-301a-5p, hsa-miR-626, hsa-miR-548y, hsa-miR-203a-5p, hsa-miR-548e-5p, hsa-miR-585-3p, hsa-miR-378h, hsa-miR-1323, hsa-miR-183-5p, hsa-miR-200a-3p, hsa-miR-888-5p, hsa-miR-199a-3p+hsa-miR-199b-3p). Among these 13 miRNAs, one (i.e., hsa-miR-203a-5p) was also identified in a prior study, with significantly different expression levels between children with and without PPCS. Conclusion Our results from the longitudinal assessment of miRNAs indicate that the expression levels of 13 salivary miRNAs differ over time post-injury in concussed children with vs. without PPCS. Salivary miRNAs may be a promising biomarker for PPCS in children, although replication studies are needed.

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