# Subventricular Zone‐on‐a‐Chip: A Model to Study Neurogenesis Disruption in Neonatal Intraventricular Hemorrhage

## TL;DR

A lab model of the brain's subventricular zone is developed to study how bleeding in preterm infants disrupts brain cell growth and to identify potential treatments.

## Contribution

The development of a human SVZ-on-a-chip model to study IVH and the identification of IL1B as a potential therapeutic target.

## Key findings

- Exposure to hemorrhagic CSF and RBCL activates inflammatory pathways in fetal astrocytes and endothelial cells.
- IL1B is upregulated following exposure to IVH-related factors and shows a partially protective role in neurogenesis.
- The SVZ-on-a-chip model is a powerful tool for studying IVH pathology and testing interventions.

## Abstract

Intraventricular hemorrhage (IVH) in preterm infants disrupts neurogenesis in the subventricular zone (SVZ), a key neurogenic niche, yet no effective treatments exist. This work develops a human SVZ‐on‐a‐chip model to investigate the inflammatory response in IVH and its impact on neurogenesis. Using this platform, this work examines the effects of red blood cell lysate (RBCL) and hemorrhagic cerebrospinal fluid (CSF) from preterm infants with IVH on SVZ cells. Transcriptomic analysis reveal activation of inflammatory pathways in fetal astrocytes and brain microvascular endothelial cells exposed to hemoglobin isoforms. Notably, interleukin‐1B (IL1B) is upregulated following RBCL and hemorrhagic CSF exposure. To probe its role, this work applies an IL1 receptor antagonist, which demonstrate that IL1B has a partially protective influence on neurogenesis. These findings highlight the SVZ‐on‐a‐chip as a powerful tool for studying IVH pathology and emphasize the role of inflammation in regulating neurogenesis. IL1B emerges as a potential therapeutic target, offering new avenues for intervention. This study advances the understanding of IVH and lays the groundwork for developing strategies to protect the developing brain.

A human subventricular zone‐on‐a‐chip is developed to model intraventricular hemorrhage (IVH) in preterm infants. This platform enables the study of inflammation‐driven neurogenic disruption. Exposure to hemorrhagic cerebrospinal fluid and red blood cell lysate activated inflammatory pathways, with IL1B emerging as a key mediator. This study establishes a powerful tool for investigating IVH pathology and potential therapeutic targets. Created with Biorender.com.