Evidence map›Paper›PMID 39661396›Full record

ArticleEpilepsia2025

Plasma microRNAs as prognostic biomarkers for development of severe epilepsy after experimental traumatic brain injury-EpiBioS4Rx Project 1 study.

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

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
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.

Mette HeiskanenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.ORCID https://orcid.org/0000-0003-1624-5240
Xavier Ekolle Ndode-EkaneA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.ORCID https://orcid.org/0000-0001-5682-5632
Idrish AliDepartment of Neuroscience, Monash University, Melbourne, Victoria, Australia.ORCID https://orcid.org/0000-0002-0971-4654
Cesar Santana-GomezDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.ORCID https://orcid.org/0000-0001-9163-5615
Noora PuhakkaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.ORCID https://orcid.org/0000-0001-6151-3510
Shalini Das GuptaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Pedro AndradeA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Riikka ImmonenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Pablo Casillas-EspinosaDepartment of Neurology, Alfred Health, Melbourne, Victoria, Australia.ORCID https://orcid.org/0000-0002-6199-9415
Eppu ManninenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.ORCID https://orcid.org/0000-0002-9353-6079
Gregory SmithUCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine, & UCLA Intellectual and Developmental Disabilities Research Center, University of California at Los Angeles, Los Angeles, California, USA.
Rhys D BradyDepartment of Neurology, Alfred Health, Melbourne, Victoria, Australia.
Juliana SilvaDepartment of Neurology, Alfred Health, Melbourne, Victoria, Australia.ORCID https://orcid.org/0000-0002-2146-4221
Emma BraineDepartment of Neurology, Alfred Health, Melbourne, Victoria, Australia.
Matt HudsonDepartment of Neurology, Alfred Health, Melbourne, Victoria, Australia.
Glen R YamakawaDepartment of Neurology, Alfred Health, Melbourne, Victoria, Australia.
Nigel C JonesDepartment of Neuroscience, Monash University, Melbourne, Victoria, Australia.ORCID https://orcid.org/0000-0002-1080-8439
Sandy R ShultzDepartment of Neuroscience, Monash University, Melbourne, Victoria, Australia.
Neil G HarrisUCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine, & UCLA Intellectual and Developmental Disabilities Research Center, University of California at Los Angeles, Los Angeles, California, USA.ORCID https://orcid.org/0000-0002-1965-6750
David K WrightDepartment of Neurology, Alfred Health, Melbourne, Victoria, Australia.
Olli GröhnA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Richard J StabaDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Terence J O'BrienDepartment of Neuroscience, Monash University, Melbourne, Victoria, Australia.
Asla PitkänenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.ORCID https://orcid.org/0000-0002-8163-5416

Funding

The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Public Engagement CoreU54NS100064 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ENGEL, JEROME NONE, GALANOPOULOU, ARISTEA S · 2017 to 2021
$21.7M
NIH HHS U54NS100064
6 · The paper itself

Abstract

objectiveTo test a hypothesis that acutely regulated plasma microRNAs (miRNAs) can serve as prognostic biomarkers for the development of post-traumatic epilepsy (PTE).

methodsAdult male Sprague-Dawley rats (n = 245) were randomized to lateral fluid-percussion-induced traumatic brain injury (TBI) or sham operation at three study sites (Finland, Australia, United States). Video-electroencephalography (vEEG) was performed on the seventh post-injury month to detect spontaneous seizures. Tail vein plasma collected 48 h after TBI for miRNA analysis was available from 209 vEEG monitored animals (45 sham, 164 TBI [32 with epilepsy]). Based on small RNA sequencing and previous data, the seven most promising brain enriched miRNAs (miR-183-5p, miR-323-3p, miR-434-3p, miR-9a-3p, miR-124-3p, miR-132-3p, and miR-212-3p) were validated by droplet digital polymerase chain reaction (ddPCR).

resultsAll seven plasma miRNAs differentiated between TBI and sham-operated rats. None of the seven miRNAs differentiated TBI rats that did and did not develop epilepsy (p > .05), or rats with ≥3 vs <3 seizures in a month (p > .05). However, miR-212-3p differentiated rats that developed epilepsy with seizure clusters (i.e., ≥3 seizures within 24 h) from those without seizure clusters (.34 ± .14 vs .60 ± .34, adj. p < .05) with an area under the curve (AUC) of .81 (95% confidence interval [CI] .65-.97, p < .01, 64% sensitivity, 95% specificity). Lack of elevation in miR-212-3p also differentiated rats that developed epilepsy with seizure clusters from all other TBI rats (n = 146, .34 ± .14 vs .55 ± .31, p < .01) with an AUC of .74 (95% CI .61-.87, p < .01, 82% sensitivity, 62% specificity). Glmnet analysis identified a combination of miR-212-3p and miR-132-3p as an optimal set to differentiate TBI rats with vs without seizure clusters (cross-validated AUC .75, 95% CI .47-.92, p < .05). SIGNIFICANCE: miR-212-3p alone or in combination with miR-132-3p shows promise as a translational prognostic biomarker for the development of severe PTE with seizure clusters.

Indexed as

Brain Injuries, TraumaticEpilepsy, Post-TraumaticMicroRNAsAnimalsBiomarkersDisease Models, AnimalElectroencephalographyMalePrognosisRatsRats, Sprague-DawleyBiomarkersMicroRNAsharmonizationlateral fluid‐percussionpost‐traumatic epilepsypreclinicalreceiver‐operating characteristic analysisvideo‐EEG monitoring

Identifiers

PMID39661396
PMCPMC11908664

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.