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Updated: Jun 5, 2025
Use of a Wireless Video-EEG System to Monitor Epileptiform Discharges Following Lateral Fluid-Percussion Induced Traumatic Brain Injury
Published on: June 21, 2019
Plasma microRNAs as prognostic biomarkers for development of severe epilepsy after experimental traumatic brain
Mette Heiskanen1, Xavier Ekolle Ndode-Ekane1, Idrish Ali2,3,4
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Objective:
To test a hypothesis that acutely regulated plasma microRNAs (miRNAs) can serve as prognostic biomarkers for the development of post-traumatic epilepsy (PTE).
Methods:
Adult 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).
Results:
All 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.
Insights
Plasma microRNAs (miRNAs) show potential for predicting severe post-traumatic epilepsy (PTE). miR-212-3p and miR-132-3p can identify rats with seizure clusters after traumatic brain injury (TBI).
Area of Science:
- Neuroscience
- Biomarker Discovery
- Molecular Biology
Background:
- Post-traumatic epilepsy (PTE) is a debilitating condition following traumatic brain injury (TBI).
- Identifying reliable prognostic biomarkers for PTE development is crucial for timely intervention.
- Plasma microRNAs (miRNAs) are emerging as potential biomarkers due to their stability and accessibility.
Purpose of the Study:
- To investigate whether acutely regulated plasma miRNAs can serve as prognostic biomarkers for PTE.
- To identify specific miRNAs that can predict the development of spontaneous seizures and seizure severity after TBI.
- To evaluate the translational potential of these miRNA biomarkers in a preclinical TBI model.
Main Methods:
- Adult male Sprague-Dawley rats underwent TBI or sham operations.
- Video-electroencephalography (vEEG) monitored seizure activity for seven months post-injury.
- Plasma miRNA levels (miR-183-5p, miR-323-3p, miR-434-3p, miR-9a-3p, miR-124-3p, miR-132-3p, and miR-212-3p) were analyzed using droplet digital PCR (ddPCR).
Main Results:
- All seven tested plasma miRNAs differentiated between TBI and sham rats.
- None of the miRNAs predicted the overall development of epilepsy or seizure frequency.
- miR-212-3p alone and a combination of miR-212-3p and miR-132-3p effectively differentiated rats with seizure clusters (≥3 seizures within 24h) from those without.
- High diagnostic accuracy (AUC up to 0.81) was observed for miR-212-3p in identifying seizure clusters.
Conclusions:
- miR-212-3p and miR-132-3p show promise as translational prognostic biomarkers for severe PTE characterized by seizure clusters.
- These miRNAs could aid in identifying individuals at high risk for developing severe seizure activity post-TBI.
- Further research is warranted to validate these findings in human clinical settings.
