Saliva microRNA Biomarkers of Cumulative Concussion

Abstract

Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated in concussion pathophysiology, would provide insights about the molecular cascade resulting from recurrent concussions. This hypothesis was tested in a case-control study involving 13 former professional football athletes with a history of recurrent concussion, and 18 age/sex-matched peers. Molecules of interest were further validated in a cross-sectional study of 310 younger individuals with a history of no concussion (n = 230), a single concussion (n = 56), or recurrent concussions (n = 24). There was no difference in neurocognitive performance between the former professional athletes and their peers, or among younger individuals with varying concussion exposures. However, younger individuals without prior concussion outperformed peers with prior concussion on three balance assessments. Twenty salivary miRNAs differed (adj. p < 0.05) between former professional athletes and their peers. Two of these (miR-28-3p and miR-339-3p) demonstrated relationships (p < 0.05) with the number of prior concussions reported by younger individuals. miR-28-3p and miR-339-5p may play a role in the pathophysiologic mechanism involved in cumulative concussion effects.

Defining Biological Phenotypes of Mild Traumatic Brain Injury Using Saliva MicroRNA Profiles

“…In this investigation, using 22 salivary miRNAs previously implicated in concussion, we identified 10 distinct biological clusters. These clusters display miRNA perturbations that mirror trends from previous studies, 9–16 and each cluster is associated with unique biological pathways that have been implicated in concussion pathophysiology. With regard to medical/demographic characteristics, there were differences among clusters in age, days post-injury (of saliva collection), and history of prior concussions, indicating that miRNA profiles may be sensitive to acute changes following injury and, perhaps, cumulative concussion effects.…”

“…Increasing evidence suggests that salivary microRNA (miRNA) levels may reflect underlying biological changes following concussion. Saliva miRNA levels change after head impacts, 9 , 10 differentiate individuals with concussion from non-concussed peers, 11 and display longitudinal patterns that mirror recovery trajectories. 12 These patterns may be useful in diagnosing concussion, 13-15 or predicting the duration of symptoms.…”

Peripheral microRNA alteration and pathway signaling after mild traumatic brain injur

“…However, the published pathways were derived from a single database, e.g., KEGG or Ingenuity Pathway analysis, respectively, leading to only partial results due to small overlap across pathway databases (Rahmati et al 2017). Despite this methodological limitation the mTOR, TGF-beta, IGF1R, neurotrophin and inflammatory signaling represent major overlap with findings of our meta-analysis and support their involvement in post mTBI conditions by multiple evidence (Qin et al 2018;Atif and Hicks 2019;Devoto et al 2020;Hicks et al 2020a;Di Pietro et al 2021).…”

The Effects of Physical Exercise on Saliva Composition: A Comprehensive Review

“…Salivary microRNAs can reflect critical biological processes related to a trauma, such as hypoxia, neurogenesis, axon repair and cell death. MicroRNAs, expressed from the saliva, seem to be an accurate non-invasive alternative to diagnose a traumatic brain injury due to a concussion [ 68 , 69 ].…”