Elevated Pro-Inflammatory Cell-Free MicroRNA Levels in Cerebrospinal Fluid of Premature Infants after Intraventricular Hemorrhage
| Autor: | Fejes, Zsolt, Erdei, Judit, Pócsi, Marianna, Takai, Jun, Jeney, Viktória, Nagy, Andrea, Varga, Alíz, Bácsi, Attila, Bognár, László, Novák, László, Kappelmayer, János, Nagy, Béla |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
microRNA Infant Newborn oxidized hemoglobin Infant intraventricular hemorrhage Article Infant Newborn Diseases cerebrospinal fluid Cell Line lcsh:Chemistry lcsh:Biology (General) lcsh:QD1-999 inflammation Humans Female Circulating MicroRNA heme lcsh:QH301-705.5 Biomarkers Infant Premature Cerebral Hemorrhage |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 6870, p 6870 (2020) International Journal of Molecular Sciences Volume 21 Issue 18 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | 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 &ldquo spike-in&rdquo 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-&alpha 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. |
| Databáze: | OpenAIRE |
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