Abstract Number: PB1249
Meeting: ISTH 2020 Congress
Background: Intraventricular hemorrhage (IVH) is a frequent complication of prematurity that is associated with high neonatal mortality and increased risk of neurodevelopmental impairment. In IVH, extravasation of red blood cells (RBCs) is followed by RBC lysis, oxidation of extracellular hemoglobin (Hb) and local inflammation in the subarachnoid space. We recently described elevated cell-free miRNA levels in cerebrospinal fluid (CSF) of preterm infants with IVH.
Aims: We have further characterized the relationship between oxidized Hb induced inflammatory response and CSF miRNA expression after IVH.
Methods: CSF samples were analyzed in 47 preterm infants at the gestational age of 28.2±3.2 weeks with grade III or IV IVH vs. clinical controls (n=14). miRNAs were isolated with miRNeasy kit, and miR-223, miR-155, and miR-181b were quantified by RT-qPCR after normalization to “spike-in” cel-miR-39. Oxidized Hb and total heme levels were determined by spectrophotometry. Concentrations of IL-8, VCAM-1, ICAM-1 and E-selectin were measured by ELISA. In vitro controlled hemolysis experiment was performed to investigate whether these miRNAs were released from RBCs upon IVH.
Results: Expression of miR-223, miR-155 and miR-181b and the levels of oxidized Hb/total heme with IL-8 were the highest in CSF samples obtained between days 1-14 after the onset of IVH vs. controls and were significantly decreased by post-IVH days 29-49. Significant correlation was observed between these miRNAs, oxidized Hb and soluble adhesion molecules levels. During follow-up, oxidized Hb was eliminated with attenuated miRNAs and VCAM-1/ICAM-1/E-selectin expression in CSF. miR-223 indicated the presence of oxidized Hb in CSF (ROC-AUC value: 0.745 [95% CI 0.597-0.892]; p=0.007). Importantly, these miRNAs remained unaffected by increasing degree of artificial hemolysis in vitro excluding their RBC origin.
Conclusions: Hb oxidation induces CSF miRNA expression during inflammatory response in preterm infants with IVH. These miRNAs may serve as potential CSF biomarkers to monitor clinical conditions after IVH.
To cite this abstract in AMA style:Fejes Z, Erdei J, Takai J, Jeney V, Nagy A, Bácsi A, Bognár L, Novák L, Kappelmayer J, BN. Inflammation Associated Cell-Free microRNA Levels in Cerebrospinal Fluid of Premature Infants Upon Intraventricular Hemorrhage [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/inflammation-associated-cell-free-microrna-levels-in-cerebrospinal-fluid-of-premature-infants-upon-intraventricular-hemorrhage/. Accessed November 26, 2020.
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