Expression profile of plasma microRNAs and their roles in diagnosis of mild to severe traumatic brain injury

Abstract

Traumatic brain injury (TBI) is associated with trauma-related death. In this study, we evaluated differences in the expression of plasma microRNAs (miRNAs) in patients with different degrees of TBI, and explored the potential of miRNAs for use as diagnostic TBI biomarkers. The miRNA microarray results showed upregulation of 65, 33, and 16 miRNAs and downregulation of 29, 27, and 6 miRNAs in patients with mild, moderate, and severe TBI, respectively, compared with healthy controls. Thirteen miRNAs (seven upregulated and six downregulated) were found to be present in all TBI groups. Seven upregulated miRNAs were selected for validation in an enlarged cohort of samples and showed good diagnostic accuracy. The expression levels of miR-3195 and miR-328-5p were higher in the severe TBI group than in the mild and moderate TBI groups. In summary, our study demonstrates different expression profiles in plasma miRNAs among patients with mild to severe TBI. A subset of seven miRNAs can be used for diagnosis of TBI. Moreover, miR-3195 and miR-328-5p may be utilized during diagnosis to distinguish mild and moderate TBI from severe TBI.

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

“…Redell and colleagues implemented miRNA microarrays and found significant changes in the levels of miR‐16, miR‐92a, and miR‐765 in plasma after TBI, demonstrating that circulating miRNAs are altered after TBI (Redell et al ). Bhomia et al () found that the identified 10 serum miRNAs can be used for the diagnosis of mild and moderate TBI as well as sTBI, Recently, Qin et al () screened and confirmed that miRNAs were potential biomarkers for the diagnosis and prognosis of TBI using miRNA microarrays. However, a limited number of TBI patients were included in those studies.…”

“…However, whether these potential biomarkers play a role in the pathological process of the nervous system is still rarely reported. Moreover, most existing studies are either based on a limited number of patients, only focus on a few specific miRNAs or provide no prognostic results, which may partially explain some of the discrepancies observed (Redell et al ; Bhomia et al ; Yang et al ; Qin et al ). Recently, Di Pietro et al () screened miRNAs and validated that they were potential biomarkers for the diagnosis and prognosis of TBI using TaqMan Low Density Array (TLDA).…”

Bioinformatic analysis of brain-specific miRNAs for identification of candidate traumatic brain injury blood biomarkers

“…The experimental strategy employed in this investigation has several distinct advantages over those employed in the small number of large-scale miRNA biomarker discovery analyses performed in TBI to date. Most notably, PREPRINT 6 prior investigations have identified candidate miRNAs by high-throughput comparisons of circulating miRNAs between TBI patients and healthy controls [20,[24][25][26]. Thus, it is unclear whether the miRNAs identified in these studies exhibit elevation in blood which are specific to brain injury, or just trauma in general.…”

Chronic Regulation of miR-124-3p in the Perilesional Cortex after Experimental and Human TBI

“…TBI regulates brain miRNA expression acutely [14][15][16][17], and some miRNAs remain regulated chronically-months to years after TBI [18,19]. Dysregulated miRNA levels are reported in the cortex [9,14,[20][21][22], hippocampus [15,16,18,19,[23][24][25][26][27], and plasma [28][29][30]. Only a few studies, however, have addressed miRNA expression in patients with TBI [13,19,23,28], highlighting the gap between preclinical and clinical studies.…”

“…Dysregulated miRNA levels are reported in the cortex [9,14,[20][21][22], hippocampus [15,16,18,19,[23][24][25][26][27], and plasma [28][29][30]. Only a few studies, however, have addressed miRNA expression in patients with TBI [13,19,23,28], highlighting the gap between preclinical and clinical studies. Our previous study showed that TBI results in miR-124-3p downregulation in both rat and human dentate gyrus, making this miRNA an interesting subject for further study.miR-124 is the most abundant microRNA in the brain, accounting for 25-48% of all brain miRNA pool [31].…”