Abstract

Following an intraventricular hemorrhage (IVH), red blood cell lysis and hemoglobin (Hb) oxidation with the release of heme can cause sterile neuroinflammation. In this study, we measured Hb derivates and cellular adhesion molecules ICAM-1 and VCAM-1 with cell-free miRNAs in cerebrospinal fluid (CSF) samples obtained from Grade-III and Grade-IV preterm IVH infants (IVH-III and IVH-IV, respectively) at multiple time points between days 0–60 after the onset of IVH. Furthermore, human choroid plexus epithelial cells (HCPEpiCs) were incubated with IVH and non-IVH CSF (10 v/v %) for 24 h in vitro to investigate the IVH-induced inflammatory response that was investigated via: (i) HMOX1, IL8, VCAM1, and ICAM1 mRNAs as well as miR-155, miR-223, and miR-181b levels by RT-qPCR; (ii) nuclear translocation of the NF-κB p65 subunit by fluorescence microscopy; and (iii) reactive oxygen species (ROS) measurement. We found a time-dependent alteration of heme, IL-8, and adhesion molecules which revealed a prolonged elevation in IVH-IV vs. IVH-III with higher miR-155 and miR-181b expression at days 41–60. Exposure of HCPEpiCs to IVH CSF samples induced HMOX1, IL8, and ICAM1 mRNA levels along with increased ROS production via the NF-κB pathway activation but without cell death, as confirmed by the cell viability assay. Additionally, the enhanced intracellular miR-155 level was accompanied by lower miR-223 and miR-181b expression in HCPEpiCs after CSF treatment. Overall, choroid plexus epithelial cells exhibit an abnormal cell phenotype after interaction with pro-inflammatory CSF of IVH origin which may contribute to the development of later clinical complications in preterm IVH.

Highlights

  • We found that intraventricular hemorrhage (IVH)-IV, but not IVH as Grade III (IVH-III) cerebrospinal fluid (CSF), significantly affected cell viability compared to the untreated baseline samples (p = 0.0279)

  • ICAM1 (p = 0.0054) messenger RNA (mRNA) levels that were induced by IVH CSF (Figure 8A–C). These results suggest that the pro-inflammatory components accumulated in the CSF after the onset of IVH promoted a remarkable inflammatory response and cellular activation in choroid plexus epithelial cells via the NF-κB pathway

  • It has been known for a long time that inflammation has a critical role in the pathomechanism of IVH-induced brain injury that may lead to irreversible neurodevelopmental complications, especially in those born before the 32 weeks of gestation [3,24]

Read more

Summary

Introduction

An intraventricular hemorrhage (IVH) is a severe, frequently seen complication in premature infants that results in an increased risk of neonatal mortality and neurodevelopmental impairments [1]. IVH affects about 15–20% of preterm infants with a very low birth weight (

Objectives
Methods
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call