{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T08:38:38Z","timestamp":1770539918748,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T00:00:00Z","timestamp":1600473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intraventricular hemorrhage (IVH) represents a high risk of neonatal mortality and later neurodevelopmental impairment in prematurity. IVH is accompanied with inflammation, hemolysis, and extracellular hemoglobin (Hb) oxidation. However, microRNA (miRNA) expression in cerebrospinal fluid (CSF) of preterm infants with IVH has been unknown. Therefore, in the present study, candidate pro-inflammatory cell-free miRNAs were analyzed in CSF samples from 47 preterm infants with grade III or IV IVH vs. clinical controls (n = 14). miRNAs were quantified by RT-qPCR, normalized to \u201cspike-in\u201d cel-miR-39. Oxidized Hb and total heme levels were determined by spectrophotometry as well as IL-8, VCAM-1, ICAM-1, and E-selectin concentrations by ELISA. To reveal the origin of the investigated miRNAs, controlled hemolysis experiments were performed in vitro; in addition, human choroid plexus epithelial cell (HCPEpiC) cultures were treated with metHb, ferrylHb, heme, or TNF-\u03b1 to replicate IVH-triggered cellular conditions. Levels of miR-223, miR-155, miR-181b, and miR-126 as well as Hb metabolites along with IL-8 were elevated in CSF after the onset of IVH vs. controls. Significant correlations were observed among the miRNAs, oxidized Hb forms, and the soluble adhesion molecules. During the post-IVH follow-up, attenuated expression of miRNAs and protein biomarkers in CSF was observed upon elimination of Hb metabolites. These miRNAs remained unaffected by a series of artificially induced hemolysis, which excluded red blood cells as their origin, while stimulation of HCPEpiCs with oxidized Hb fractions and heme resulted in increased extracellular miRNA levels in the cell culture supernatant. Overall, the hemorrhage-induced CSF miRNAs reflected inflammatory conditions as potential biomarkers in preterm IVH.<\/jats:p>","DOI":"10.3390\/ijms21186870","type":"journal-article","created":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T07:06:09Z","timestamp":1600499169000},"page":"6870","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Elevated Pro-Inflammatory Cell-Free MicroRNA Levels in Cerebrospinal Fluid of Premature Infants after Intraventricular Hemorrhage"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1387-2970","authenticated-orcid":false,"given":"Zsolt","family":"Fejes","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"K\u00e1lm\u00e1n Laki Doctoral School of Biomedical and Clinical Sciences, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1652-4506","authenticated-orcid":false,"given":"Judit","family":"Erdei","sequence":"additional","affiliation":[{"name":"MTA-DE Lend\u00fclet Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"P\u00f3csi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4942-7091","authenticated-orcid":false,"given":"Vikt\u00f3ria","family":"Jeney","sequence":"additional","affiliation":[{"name":"MTA-DE Lend\u00fclet Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Al\u00edz","family":"Varga","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"B\u00e1csi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Bogn\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Nov\u00e1k","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1nos","family":"Kappelmayer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"K\u00e1lm\u00e1n Laki Doctoral School of Biomedical and Clinical Sciences, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"B\u00e9la","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"K\u00e1lm\u00e1n Laki Doctoral School of Biomedical and Clinical Sciences, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1080\/14767050902769982","article-title":"Impact of mode of delivery on neonatal complications: Trends between 1997 and 2005","volume":"22","author":"Jain","year":"2009","journal-title":"J. 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