Mechanistically informed circulating biomarkers are associated with acquired epilepsy after neonatal brain injury

作者：Adam L. Numis, Renée A. Shellhaas, Janet S. Soul, Marisa Gardner, Courtney J. Wusthoff, Giulia M. Benedetti, Clara Di Germanio, Theo K. Bammler, David J. Erle, Walter L. Eckalbar, Charles E. McCulloch, Patrick J. Heagerty, Thomas R. Wood, Yvonne W. Wu, Sandra E. Juul, D Lowenstein, Hannah C. Glass, the Neonatal Seizure Registry Study Group, Tayyba Anwar, Madison Berl, Catherine J. Chu, Linda S. Franck, Monica E. Lemmon, Betsy Thomas, Cameron Thomas, Kaashif A. Ahmad, Sonia L. Bonifacio, Bryan A. Comstock, Fernando F. Gonzalez, Nathalie Maitre, Shavonne L. Massey, Dennis E. Maycock, Ulrike Mietzsch, Niranjana Natarajan, Gregory M. Sokol, Cameron Thomas, Krisa P. Van Meurs · 发表于：Journal of Neuroinflammation · 年份：2026 · DOI：10.1186/s12974-026-03853-9 · 研究领域：Neonatal and fetal brain pathology、Epilepsy research and treatment、Anesthesia and Neurotoxicity Research

BACKGROUND: Acute provoked neonatal seizures are a major risk factor for acquired epilepsy, yet clinicians lack reliable tools to identify neonates at highest risk. Preclinical data implicate innate immune activation and neuronal injury as key drivers of epileptogenesis, suggesting blood-based biomarkers could provide mechanistic insight and prognostic utility. We sought to identify biomarkers of epileptogenesis in neonates with acute provoked seizures after brain injury using multicenter cohorts. METHODS: We conducted a prospective, multi-cohort analysis across two independent studies. NSR-RISE enrolled neonates with EEG-confirmed acute provoked seizures of diverse etiologies. The HEAL trial enrolled neonates with hypoxic-ischemic encephalopathy; analyses were limited to those with seizures. Plasma proteins were quantified 48-96 h after seizure onset. Associations with acquired epilepsy by 24-months were evaluated using log-link models with robust standard errors and false-discovery rate correction (FDR < 0.05). Significant proteins were added to models including established clinical predictors (≥ 3 days of EEG seizures and abnormal neurological examination at discharge). Exploratory pathway enrichment used KEGG databases. NSR-RISE participants also underwent plasma microRNA (miRNA) sequencing with integrative pathway analyses. RESULTS: Among 35 neonates in NSR-RISE, 7 (20%) developed epilepsy; among 40 neonates in HEAL, 6 (15%) developed epilepsy. Across both cohorts, neona...