TY - JOUR A1 - Raoof, Rana A1 - Bauer, Sebastian A1 - El Naggar, Hany A1 - Connolly, Niamh M. C. A1 - Brennan, Gary P. A1 - Brindley, Elizabeth A1 - Hill, Thomas A1 - McArdle, Hazel A1 - Spain, Elaine A1 - Forster, Robert J. A1 - Prehn, Jochen H. M. A1 - Hamer, Hajo A1 - Delanty, Norman A1 - Rosenow, Felix A1 - Mooney, Catherine A1 - Henshall, David C. T1 - Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy T2 - EBioMedicine N2 - Background: There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable detection in biofluids. Altered levels of circulating microRNAs have been reported in human epilepsy, but most studies collected samples from one clinical site, used a single profiling platform or conducted minimal validation. Method: Using a case-control design, we collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated findings in a large (>250) cohort of samples that included patients with psychogenic non-epileptic seizures (PNES). Findings: After profiling and validation, we identified miR-27a-3p, miR-328-3p and miR-654-3p with biomarker potential. Plasma levels of these microRNAs were also changed in a mouse model of TLE but were not different to healthy controls in PNES patients. We determined copy number of the three microRNAs in plasma and demonstrate their rapid detection using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Analysis of the microRNAs within the exosome-enriched fraction provided high diagnostic accuracy while Argonaute-bound miR-328-3p selectively increased in patient samples after seizures. In situ hybridization localized miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics predicted targets linked to growth factor signaling and apoptosis. Interpretation: This study demonstrates the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms. KW - Biofluids KW - Dissociative seizures KW - Temporal lobe epilepsy KW - Status epilepticus KW - Noncoding RNA KW - Serum Y1 - 2018 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50028 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-500288 SN - 2352-3964 N1 - © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) VL - 38 SP - 127 EP - 141 PB - Elsevier CY - Amsterdam [u. a.] ER -