Evidence map›Paper›PMID 40992209›Full record

ArticleEpilepsy research2025

Standardization of preclinical methodologies for discovery and validation of circulating microRNA biomarkers for post-traumatic epileptogenesis - Lessons learned from the EpiBioS4Rx Project 1.

Noora Puhakka, Mette Heiskanen, Xavier Ekolle Ndode-Ekane, Idrish Ali, Cesar Santana-Gomez, Shalini Das Gupta, Meheli Banerjee, Pedro Andrade, Riikka Immonen, Pablo Casillas-Espinosa and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsy research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Noora PuhakkaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, Kuopio FI-70211, Finland.
Mette HeiskanenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, Kuopio FI-70211, Finland.
Xavier Ekolle Ndode-EkaneA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, Kuopio FI-70211, Finland.
Idrish AliDepartment of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Cesar Santana-GomezDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, United States.
Shalini Das GuptaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, Kuopio FI-70211, Finland.
Meheli BanerjeeA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, Kuopio FI-70211, Finland.
Pedro AndradeA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, Kuopio FI-70211, Finland.
Riikka ImmonenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, Kuopio FI-70211, Finland.
Pablo Casillas-EspinosaDepartment of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Gregory SmithUCLA Brain Injury Research Center & Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, United States.
Rhys D BradyDepartment of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Juliana SilvaDepartment of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Emma BraineDepartment of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Matthew R HudsonDepartment of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Glen R YamakawaDepartment of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Nigel C JonesDepartment of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Sandy R ShultzDepartment of Neuroscience, Monash University, Melbourne, Australia.
Neil G HarrisUCLA Brain Injury Research Center & Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, United States.
David K WrightDepartment of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Olli GröhnA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, Kuopio FI-70211, Finland.
Richard StabaDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, United States.
Terence J O'BrienDepartment of Neuroscience, Monash University, Melbourne, Australia; Department of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
Asla PitkänenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, Kuopio FI-70211, Finland. Electronic address: asla.pitkanen@uef.fi.

Funding

The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Public Engagement CoreU54NS100064 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2017 to 2021
$21.7M
The Epilepsy Bioinformatics Study (EpiBioS)P20NS080181 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ENGEL, JEROME NONE, HOVDA, DAVID A · 2012 to 2014
$1.7M
NINDS NIH HHS P20 NS080181NINDS NIH HHS U54 NS100064
6 · The paper itself

Abstract

objectiveTo analyze the success of harmonization and standardization of plasma miRNA biomarker discovery and validation for post-traumatic epilepsy (PTE) in the EpiBioS4Rx international multicenter project.

methodsAdult male Sprague-Dawley rats were randomized to lateral fluid-percussion-induced traumatic brain injury (TBI) or sham operation at three study sites (Finland, Australia, USA). Video-electroencephalogram (vEEG) was performed in the 7th post-injury month to detect spontaneous seizures. Tail vein plasma was collected at baseline and 48 h after TBI for microRNA (miRNA) analysis. Common data elements were generated to document and monitor pre-analytic activities, including housing conditions, post-injury care, blood sampling, plasma preparation, plasma quality, storage, and shipping. miRNA analysis was performed using droplet digital PCR (ddPCR) at one study site (Finland) with on-site standardized procedures.

resultsThe 2-day miRNA levels were successfully measured in 85 % (209/245) of the rats included in the final analysis cohort. Exclusions were related to small sample volume, hemolysis, and failed RNA extraction for ddPCR. Most of the pre-analytical factors leading to sample exclusions were related to non-optimal plasma pipetting. We also recognized gaps in data entry and monitoring of personnel training.

conclusionsOur study demonstrates that conducting a successful plasma miRNA biomarker analysis requires procedural harmonization between laboratories, protocol standardization, inclusion and analysis of quality controls, training of researchers, and continuous monitoring of adherence to pre-agreed protocols.

Indexed as

Brain Injuries, TraumaticCirculating MicroRNAEpilepsy, Post-TraumaticAnimalsBiomarkersDisease Models, AnimalElectroencephalographyMaleRatsRats, Sprague-DawleyBiomarkersCirculating MicroRNAHarmonizationLateral fluid-percussionMicroRNAPlasmaPost-traumatic epilepsyPreclinical

Identifiers

PMID40992209
PMCPMC13265265

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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.