Researchers find biomarkers to diagnose mild traumatic brain injury

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© Steph Freeman

Mild traumatic brain injury is difficult to detect by contemporary conventional imaging methods, but a new study from Finland has discovered that certain plasma microRNAs could serve as diagnostic biomarkers in such injuries.

In cases of mild traumatic brain injury (TBI), most patients do not exhibit visible structural damage to the brain, which could be detected by computer tomography. Even without visible structural damage, it is extremely important to diagnose mild traumatic brain injury since patients’ ability to work and their overall quality-of-life is affected.

Researchers at the University of Eastern Finland discovered the biomarkers in an animal model and they were successfully used to diagnose mild traumatic brain injury in a subgroup of patients. The study has been published in the International Journal of Molecular Sciences.

The research team said there is a major unmet medical need to identify accurate, affordable, and widely accessible diagnostic biomarkers that could be used to better diagnose patients with mild TBI, and to guide them to symptomatic, timely and rehabilitative treatment.

Blood-based biomarkers enable minimally invasive and cost-effective diagnostics. Earlier studies have shown that many biomarkers hold promise for characterising the severity of TBI, and they can provide molecular-level information about the ongoing pathological changes. In the newly published study, researchers set out to find microRNAs that could serve as biomarkers to diagnose TBI. MicroRNAs, or miRNAs, are small RNA molecules that regulate the expression of protein-coding genes. The researchers sequenced blood plasma samples from an animal model and the miRNAs showing the greatest potential on the basis of the sequencing data were selected for further, polymerase chain reaction (PCR) based analysis.

“We have been developing a suitable analysis and measurement method especially for miRNAs that can be found in small amounts in plasma, and this method is based on digital droplet PCR,” Dr Noora Puhakka from the A. I. Virtanen Institute for Molecular Sciences at the University of Eastern Finland says.

“Humans and animals share many identical miRNAs, and this makes them excellent candidates for translational studies, where results achieved in animal models are sought to be applied in humans. However, it has proven challenging to reproduce results from different studies and different sets of data. This is why assessing the quality of measurement methods, and reproducibility, is an extremely important part of biomarker research,” Puhakka said.

The objective of the newly published study was to identify plasma miRNA biomarkers that are sensitive and specific to mild traumatic brain injury in an animal model, and to explore whether they could also be used to diagnose mild traumatic brain injury in humans.

In other words, plasma miR-9a-3p and miR-136-3p proved to be potential biomarker candidates to diagnose mild traumatic brain injury both in the animal model and in patients.

“Both of these miRNAs are more abundant in the brain than in other tissues, and their elevated levels in plasma could possibly be due to brain injury and the level of its seriousness. However, further research in larger patient cohorts is still needed,” Puhakka said.

The study was conducted by Professor Asla Pitkänen’s research group in collaboration with Kuopio University Hospital. Traditional laboratory analyses were extensively supplemented by modern bioinformatics and machine learning methods.

Das Gupta, Shalini; Ciszek, Robert; Heiskanen, Mette; Lapinlampi, Niina; Kukkonen, Janne; Leinonen, Ville; Puhakka, Noora; Pitkänen, Asla. 2021. 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. 22, no. 4: 1563. https://doi.org/10.3390/ijms22041563

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