Association of Salivary MicroRNA Changes With Prolonged Concussion Symptoms

Abstract

IMPORTANCE Approximately one-third of children who experience a concussion develop prolonged concussion symptoms. To our knowledge, there are currently no objective or easily administered tests for predicting prolonged concussion symptoms. Several studies have identified alterations in epigenetic molecules known as microRNAs (miRNAs) following traumatic brain injury. No studies have examined whether miRNA expression can detect prolonged concussion symptoms. OBJECTIVE To evaluate the efficacy of salivary miRNAs for identifying children with concussion who are at risk for prolonged symptoms. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study at the Penn State Medical Center observed 52 patients aged 7 to 21 years presenting for evaluation of concussion within 14 days of initial head injury, with follow-up at 4 and 8 weeks. EXPOSURES All patients had a clinical diagnosis of concussion. MAIN OUTCOMES AND MEASURES Salivary miRNA expression was measured at the time of initial clinical presentation in all patients. Patients with a Sport Concussion Assessment Tool (SCAT3) symptom score of 5 or greater on self-report or parent report 4 weeks after injury were designated as having prolonged symptoms. RESULTS Of the 52 included participants, 22 (42%) were female, and the mean (SD) age was 14 (3) years. Participants were split into the prolonged symptom group (n = 30) and acute symptom group (n = 22). Concentrations of 15 salivary miRNAs spatially differentiated prolonged and acute symptom groups on partial least squares discriminant analysis and demonstrated functional relationships with neuronal regulatory pathways. Levels of 5 miRNAs (miR-320c-1, miR-133a-5p, miR-769-5p, let-7a-3p, and miR-1307-3p) accurately identified patients with prolonged symptoms on logistic regression (area under the curve, 0.856; 95% CI, 0.822-0.890). This accuracy exceeded accuracy of symptom burden on child (area under the curve, 0.649; 95% CI, 0.388-0.887) or parent (area under the curve, 0.562; 95% CI, 0.219-0.734) SCAT3 score. Levels of 3 miRNAs were associated with specific symptoms 4 weeks after injury; miR-320c-1 was associated with memory difficulty (R, 0.55; false detection rate, 0.02), miR-629 was associated with headaches (R, 0.47; false detection rate, 0.04), and let-7b-5p was associated with fatigue (R, 0.45; false detection rate, 0.04). CONCLUSIONS AND RELEVANCE Salivary miRNA levels may identify the duration and character of concussion symptoms. This could reduce parental anxiety and improve care by providing a tool for concussion management. Further validation of this approach is needed.

Potential Associations Among Alteration of Salivary miRNAs, Saliva Microbiome Structure, and Cognitive Impairments in Autistic Children

“…Moreover, the levels of miR-29a-3p were decreased in whole blood [ 76 ] and those of miR-141-3p in serum of Parkinson’s patients [ 77 ]. Levels of let-7b-5p were decreased in the saliva of children with mild traumatic brain injury [ 78 ]. Intriguingly, a downregulation of miR-451a and miR-16-5p was also identified in peripheral blood of ASD children [ 79 ].…”

Saliva microRNA Biomarkers of Cumulative Concussion

“…Previously, we showed that perturbation in miRNA signaling after traumatic brain injury results in overlapping miRNA profiles in cerebrospinal fluid and saliva [ 31 ]. Further, we demonstrated that disruptions in salivary miRNA levels can persist for weeks after initial injury [ 32 ], and predict the occurrence of persistent post-concussive symptoms [ 33 ]. The purpose of the current study was to determine whether non-invasive salivary measurement of miRNAs could provide insights into the pathobiology of repetitive concussions among professional football athletes.…”

SPAG5‐AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway

“…We sorted out miR‐769‐5p from 10 miRNAs shared by SPAG5‐AS1 and YY1 because it was downregulated by HG in HPCs and interacted with SPAG5‐AS1. Former studies showed that miR‐769‐5p participated in prolonged concussion symptoms and acted a predictor of lung cancer patient survival . However, this was the first time for miR‐769‐5p to be related to HG‐induced podocyte injury.…”