{"doi":"10.1111/epi.18219","title":"Plasma <scp>microRNAs</scp> as prognostic biomarkers for development of severe epilepsy after experimental traumatic brain injury— <scp>EpiBioS4Rx</scp> Project 1 study","abstract":"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.","journal":"Epilepsia","year":2024,"id":429085,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8629,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1053753,"name":"Xavier Ekolle Ndode‐Ekane","orcid":"0000-0001-5682-5632","position":1,"is_corresponding":false},{"id":1053754,"name":"Idrish Ali","orcid":"0000-0002-0971-4654","position":2,"is_corresponding":false},{"id":784914,"name":"Cesar Santana‐Gomez","orcid":"0000-0001-9163-5615","position":3,"is_corresponding":false},{"id":1053759,"name":"Noora Puhakka","orcid":"0000-0001-6151-3510","position":4,"is_corresponding":false},{"id":1231191,"name":"Shalini Das Gupta","orcid":"0000-0002-3613-0398","position":5,"is_corresponding":false},{"id":1053755,"name":"Pedro Andrade","orcid":"0000-0001-9118-8341","position":6,"is_corresponding":false},{"id":1053756,"name":"Riikka Immonen","orcid":"0000-0002-9855-7098","position":7,"is_corresponding":false},{"id":1053757,"name":"Pablo M. Casillas‐Espinosa","orcid":"0000-0002-6199-9415","position":8,"is_corresponding":false},{"id":1053758,"name":"Eppu Manninen","orcid":"0000-0002-9353-6079","position":9,"is_corresponding":false},{"id":1231192,"name":"Gregory S. Smith","orcid":"0000-0002-2892-5481","position":10,"is_corresponding":false},{"id":1054408,"name":"Rhys D. Brady","orcid":null,"position":11,"is_corresponding":false},{"id":1053761,"name":"Juliana Silva","orcid":"0000-0002-2146-4221","position":12,"is_corresponding":false},{"id":1054409,"name":"Emma L. Braine","orcid":null,"position":13,"is_corresponding":false},{"id":1107060,"name":"Matt Hudson","orcid":null,"position":14,"is_corresponding":false},{"id":1053763,"name":"Glenn R. Yamakawa","orcid":"0000-0003-3079-6532","position":15,"is_corresponding":false},{"id":1053764,"name":"Nigel C. Jones","orcid":"0000-0002-1080-8439","position":16,"is_corresponding":false},{"id":640058,"name":"Sandy R. Shultz","orcid":"0000-0002-2525-8775","position":17,"is_corresponding":false},{"id":642726,"name":"Neil G. Harris","orcid":"0000-0002-1965-6750","position":18,"is_corresponding":false},{"id":1048837,"name":"David Wright","orcid":"0000-0002-7535-8651","position":19,"is_corresponding":false},{"id":426005,"name":"Olli Gröhn","orcid":"0000-0003-1372-1651","position":20,"is_corresponding":false},{"id":581696,"name":"Richard J. Staba","orcid":"0000-0003-2285-5627","position":21,"is_corresponding":false},{"id":52291,"name":"Terence J. O’Brien","orcid":"0000-0002-7198-8621","position":22,"is_corresponding":false},{"id":65608,"name":"Asla Pitkänen","orcid":"0000-0002-8163-5416","position":23,"is_corresponding":false},{"id":1137458,"name":"Mette Heiskanen","orcid":"0000-0003-1624-5240","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:59:06.668462Z","pmid":"39661396","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}