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Article

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

1
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland
2
Department of Neurosurgery, Kuopio University Hospital, 70029 Kuopio, Finland
3
Institute of Clinical Medicine, University of Eastern Finland, 70210 Kuopio, Finland
*
Author to whom correspondence should be addressed.
These authors shared last authorship.
Academic Editor: Changiz Taghibiglou
Int. J. Mol. Sci. 2021, 22(4), 1563; https://doi.org/10.3390/ijms22041563
Received: 6 January 2021 / Revised: 31 January 2021 / Accepted: 1 February 2021 / Published: 4 February 2021
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. View Full-Text
Keywords: biomarker; microRNA; mild TBI; miR-9-3p; miR-136-3p; plasma; severe TBI biomarker; microRNA; mild TBI; miR-9-3p; miR-136-3p; plasma; severe TBI
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MDPI and ACS Style

Das Gupta, S.; Ciszek, R.; Heiskanen, M.; Lapinlampi, N.; Kukkonen, J.; Leinonen, V.; Puhakka, N.; Pitkänen, A. Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury. Int. J. Mol. Sci. 2021, 22, 1563. https://doi.org/10.3390/ijms22041563

AMA Style

Das Gupta S, Ciszek R, Heiskanen M, Lapinlampi N, Kukkonen J, Leinonen V, Puhakka N, Pitkänen A. Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury. International Journal of Molecular Sciences. 2021; 22(4):1563. https://doi.org/10.3390/ijms22041563

Chicago/Turabian Style

Das Gupta, Shalini, Robert Ciszek, Mette Heiskanen, Niina Lapinlampi, Janne Kukkonen, Ville Leinonen, Noora Puhakka, and Asla Pitkänen. 2021. "Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury" International Journal of Molecular Sciences 22, no. 4: 1563. https://doi.org/10.3390/ijms22041563

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