Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles

Abstract

The diagnosis and clinical management of aneurysmal subarachnoid hemorrhage (aSAH) is currently limited by the lack of accessible molecular biomarkers that reflect the pathophysiology of disease. We used microRNAs (miRNAs) as diagnostics to characterize plasma extracellular vesicles in aSAH. It is unclear whether they can diagnose and manage aSAH. Next-generation sequencing (NGS) was used to detect the miRNA profile of plasma extracellular vesicles (exosomes) in three patients with SAH and three healthy controls (HCs). We identified four differentially expressed miRNAs and validated the results using quantitative real-time polymerase chain reaction (RT-qPCR) with 113 aSAH patients, 40 HCs, 20 SAH model mice, and 20 sham mice. Exosomal miRNA NGS revealed that six circulating exosomal miRNAs were differentially expressed in patients with aSAH versus HCs and that the levels of four miRNAs (miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p) were differentially significant. After multivariate logistic regression analysis, only miR-369-3p, miR-486-3p, and miR-193b-3p enabled prediction of neurological outcomes. In a mouse model of SAH, greater expression of miR-193b-3p and miR-486-3p remained statistically significant relative to controls, whereas expression levels of miR-369-3p and miR-410-3p were lower. miRNA gene target prediction showed six genes associated with all four of these differentially expressed miRNAs. The circulating exosomes miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p may influence intercellular communication and have potential clinical utility as prognostic biomarkers for aSAH patients.

Abnormal levels of expression of microRNAs in peripheral blood of patients with traumatic brain injury are induced by microglial activation and correlated with severity of injury

“…Subsequently, these miRNAs enter the circulatory system and be easily detected [ 9 , 27 ]. Lai et al and Sheng et al independently found that the expression of hsa-miR-193b-3p in the exosomes of patients with TBI was significantly higher than that in the exosomes of healthy controls [ 9 , 12 ]. In addition, the injection of exosomes containing hsa-miR-193b-3p was found to significantly attenuate neuroinflammation in animal models of TBI [ 9 ].…”

“…Compared with patients with moderate or severe TBI without SAH, such patients with SAH have poorer outcomes. In addition, the circulating miRNA expression profiles of patients with SAH were found to be significantly different from those of healthy controls [ 12 ]. Furthermore, intravenously injected exosomes containing miR-193b-3p showed neuroprotective and anti-inflammatory effects in a mouse model of SAH induced by brain injury [ 9 ].…”

Exosomal microRNAs: implications in the pathogenesis and clinical applications of subarachnoid hemorrhage

“…The study revealed that exosomal miR-603 had significantly higher concentrations in the cerebrospinal fluid of patients with SAH, which affected vascular smooth muscle cell dysfunction ( Li et al, 2022 ). Moreover, Bing Sheng et al discovered that exosomal miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p might influence intercellular communication and have potential application as prognostic biomarkers for aneurysmal SAH patients ( Sheng et al, 2023 ). Here we summarize the predictive significance of exosomes as biomarkers ( Table 2 ).…”

“…The study revealed that exosomal miR-603 had significantly higher concentrations in the cerebrospinal fluid of patients with SAH, which affected vascular smooth muscle cell dysfunction (Li et al, 2022). Moreover, Bing might influence intercellular communication and have potential application as prognostic biomarkers for aneurysmal SAH patients (Sheng et al, 2023).…”

“…It is essential to note that exosomal miRNAs have been widely observed to exert a significant impact on the occurrence and development of SAH, significantly influencing neuronal apoptosis, cerebral microcirculation disorders, and neuroinflammation ( Zhao et al, 2019 ; Lai et al, 2020 ; Xiong et al, 2020 ). They are expected to become a novel generation of molecular diagnostic markers ( Sheng et al, 2023 ). This article summarizes the correlation between exosomal miRNA and SAH, as well as their potential benefits and application value for clinical diagnosis and treatment compared to conventional methods.…”