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

• Tác giả: Idrish Ali, Pedro Andrade, Rhys D Brady, Emma Braine, Pablo Casillas-Espinosa, Olli Gröhn, Shalini Das Gupta, Neil G Harris, Mette Heiskanen, Matt Hudson, Riikka Immonen, Nigel C Jones, Eppu Manninen, Xavier Ekolle Ndode-Ekane, Terence J O'Brien, Asla Pitkänen, Noora Puhakka, Cesar Santana-Gomez, Sandy R Shultz, Juliana Silva, Gregory Smith, Richard J Staba, David K Wright, Glen R Yamakawa
• Ngôn ngữ: eng
• Thông tin xuất bản: United States : Epilepsia , 2025
• Bộ sưu tập: NCBI
• ID: 700579

Tóm tắt

 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.