Abstract

MicroRNAs (MiRNAs) are small endogenous RNA molecules and have emerged as novel serum diagnostic biomarkers for several diseases due to their stability and detection at minute quantities. In this study, we have identified a serum miRNA signature in human serum samples of mild to severe TBI, which can be used for diagnosis of mild and moderate TBI (MMTBI). Human serum samples of MMTBI, severe TBI (STBI), orthopedic injury and healthy controls were used and miRNA profiling was done using taqman real time PCR. The real time PCR data for the MMTBI, STBI and orthopedic injury was normalized to the control samples which showed upregulation of 39, 37 and 33 miRNAs in MMTBI, STBI and orthopedic injury groups respectively. TBI groups were compared to orthopedic injury group and an up-regulation of 18 and 20 miRNAs in MMTBI and STBI groups was observed. Among these, a signature of 10 miRNAs was found to be present in both MMTBI and STBI groups. These 10 miRNAs were validated in cerebrospinal fluid (CSF) from STBI and four miRNAs were found to be upregulated in CSF. In conclusion, we identified a subset of 10 unique miRNAs which can be used for diagnosis of MMTBI and STBI.

Highlights

  • Mild TBI (MTBI) called concussion accounts for more than 77% of the total reported TBI cases in the United States[3]

  • Human serum samples of mild to moderate TBI (MMTBI) (n = 8) (GCS 9–15) and orthopedic injury patients (n = 7) who did not have head injury were collected within 24 hr of injury[23]

  • We identified that miR-202 was stably expressed among all the injury groups as well as in the control group and it was selected as endogenous control for all the subsequent experiments

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Summary

Introduction

Mild TBI (MTBI) called concussion accounts for more than 77% of the total reported TBI cases in the United States[3]. Most of the currently studied protein biomarkers have relatively low sensitivity for MTBI in individuals without detectable intracranial lesions. We reported that expression of miRNA let-7i was upregulated both in serum and CSF after exposure to mild to moderate blast overpressure wave in a rodent model[19]. The serum expression of miRNAs in response to a concussive mild injury in a closed head injury model was reported. Redell and colleagues studied the miRNA expression in human serum sample of TBI. Their results identified miR-16, miR-92a, and miR-765 as potential biomarkers of STBI with good diagnostic accuracy, the diagnostic accuracy of these markers for MTBI was limited[22]

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