Plasma Exosome-derived MicroRNAs as Novel Biomarkers of Traumatic Brain Injury in Rats

Wang, Pengcheng; Ma, Hongwei; Zhang, Yuxian; Zeng, Rong; Yu, Jiangtao; Liu, Ruining; Jin, Xiaoqing; Zhao, Yan

doi:10.7150/ijms.39667

Cited by 27 publications

(19 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, its level in normal plasma is very low, as indicated by a low copy number in naïve rats and also in the human controls in our study. Similar to our observation, another recent study identified increased miR-9a-3p levels in plasma exosomes of rats with weight-drop–induced TBI compared with sham-operated controls [ 55 ]. Elevated serum miR-9 levels were also reported in a group of American-style football players with at least six years of playing experience and 41% with previously reported concussion, in comparison with nonathlete controls [ 24 ].…”

Section: Discussionsupporting

confidence: 91%

Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury

Gupta

Ciszek

Heiskanen

et al. 2021

IJMS

View full text Add to dashboard Cite

Noninvasive, affordable circulating biomarkers for difficult-to-diagnose mild traumatic brain injury (mTBI) are an unmet medical need. Although blood microRNA (miRNA) levels are reportedly altered after traumatic brain injury (TBI), their diagnostic potential for mTBI remains inconclusive. We hypothesized that acutely altered plasma miRNAs could serve as diagnostic biomarkers both in the lateral fluid percussion injury (FPI) model and clinical mTBI. We performed plasma small RNA-sequencing from adult male Sprague–Dawley rats (n = 31) at 2 days post-TBI, followed by polymerase chain reaction (PCR)-based validation of selected candidates. miR-9a-3p, miR-136-3p, and miR-434-3p were identified as the most promising candidates at 2 days after lateral FPI. Digital droplet PCR (ddPCR) revealed 4.2-, 2.8-, and 4.6-fold elevations in miR-9a-3p, miR-136-3p, and miR-434-3p levels (p < 0.01 for all), respectively, distinguishing rats with mTBI from naïve rats with 100% sensitivity and specificity. DdPCR further identified a subpopulation of mTBI patients with plasma miR-9-3p (n = 7/15) and miR-136-3p (n = 5/15) levels higher than one standard deviation above the control mean at <2 days postinjury. In sTBI patients, plasma miR-9-3p levels were 6.5- and 9.2-fold in comparison to the mTBI and control groups, respectively. Thus, plasma miR-9-3p and miR-136-3p were identified as promising biomarker candidates for mTBI requiring further evaluation in a larger patient population.

show abstract

Section: Discussionsupporting

confidence: 91%

Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury

Gupta

Ciszek

Heiskanen

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In rodent TBI model, specific EVs miRNA expression pattern (significantly increased miR-21, miR-146, miR-7a, and miR-7b; decreased miR-212) indicates the presence of an enhancement loop among neuroinflammation and EVs [ 71 ]. In another study, around 50 exosomal miRNAs were described to be altered after TBI (31 up-regulated and 19 down-regulated) [ 72 ].…”

Section: Evs In Injury and Traumamentioning

confidence: 99%

Extracellular vesicles as mediators and markers of acute organ injury: current concepts

Weber

Franz

Marzi

et al. 2021

Eur J Trauma Emerg Surg

View full text Add to dashboard Cite

Due to the continued high incidence and mortality rate worldwide, there is a need to develop new strategies for the quick, precise, and valuable recognition of presenting injury pattern in traumatized and poly-traumatized patients. Extracellular vesicles (EVs) have been shown to facilitate intercellular communication processes between cells in close proximity as well as distant cells in healthy and disease organisms. miRNAs and proteins transferred by EVs play biological roles in maintaining normal organ structure and function under physiological conditions. In pathological conditions, EVs change the miRNAs and protein cargo composition, mediating or suppressing the injury consequences. Therefore, incorporating EVs with their unique protein and miRNAs signature into the list of promising new biomarkers is a logical next step. In this review, we discuss the general characteristics and technical aspects of EVs isolation and characterization. We discuss results of recent in vitro, in vivo, and patients study describing the role of EVs in different inflammatory diseases and traumatic organ injuries. miRNAs and protein signature of EVs found in patients with acute organ injury are also debated.

show abstract

“…In recent years, increasing evidence has indicated that miRNAs play an important role in the pathological process after TBI [29][30][31] . miRNAs have been found to be able to freely pass through the BBB to the peripheral blood via exosomes, providing a basis for miRNA as a biomarker for brain function recovery after TBI [32][33][34] . Therefore, clarifying the role of miRNAs after TBI may be helpful for formulating treatment strategies in the future.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury

et al. 2021

Cell Death Dis

View full text Add to dashboard Cite

The level of microRNA-9-5p (miRNA-9-5p) in brain tissues is significantly changed in the chronic phase after traumatic brain injury (TBI). However, the effect of miRNA-9-5p on brain function after TBI has not been elucidated. In this study, we used a controlled cortical impact (CCI) model to induce TBI in Sprague–Dawley rats. Brain microvascular endothelial cells (BMECs), astrocytes, and neurons were extracted from immature Sprague–Dawley rats and cocultured to reconstruct the neurovascular unit (NVU) in vitro. The results showed that downregulation of miRNA-9-5p in the chronic phase contributed to neurological function recovery by promoting astrocyte proliferation and increasing the release of astrocyte-derived neurotrophic factors around injured brain tissues after TBI. A dual-luciferase reporter assay validated that miRNA-9-5p was a post-transcriptional modulator of thrombospondin 2 (Thbs-2), and downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes. Furthermore, we verified that Thbs-2 can promote Notch pathway activation by directly binding to Jagged and Notch. Through in vitro experiments, we found that the expression of synaptic proteins and the number of synaptic bodies were increased in neurons in the NVU, which was constructed using astrocytes pretreated with miRNA-9-5p inhibitor. Moreover, we also found that downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes, which activated the Notch/cylindromatosis/transforming growth factor-β-activated kinase 1 pathway in neurons and promoted the expression of synaptic proteins, including post-synaptic density protein 95 and synaptotagmin. Based on these results, miRNA-9-5p may be a new promising prognostic marker and treatment target for TBI.

show abstract

Plasma Exosome-derived MicroRNAs as Novel Biomarkers of Traumatic Brain Injury in Rats

Cited by 27 publications

References 65 publications

Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury

Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury

Extracellular vesicles as mediators and markers of acute organ injury: current concepts

Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury

Contact Info

Product

Resources

About