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

Area of Science:

• Neuroscience
• Developmental Biology
• Biomedical Engineering

Background:

• Intraventricular hemorrhage (IVH) in preterm infants impairs neurogenesis in the subventricular zone (SVZ).
• Current treatments for IVH-induced neurogenesis disruption are lacking.
• Understanding the inflammatory mechanisms in IVH is crucial for developing interventions.

Purpose of the Study:

• To develop and utilize a human SVZ-on-a-chip model to investigate IVH-induced inflammation and its effects on neurogenesis.
• To examine the impact of red blood cell lysate (RBCL) and hemorrhagic cerebrospinal fluid (CSF) on SVZ cells.
• To identify potential therapeutic targets for protecting neurogenesis following IVH.

Main Methods:

• Development of a human SVZ-on-a-chip platform.
• Exposure of SVZ cells to RBCL and hemorrhagic CSF from IVH infants.
• Transcriptomic analysis to identify inflammatory pathways.
• Application of an IL1 receptor antagonist to assess the role of IL1B.

Main Results:

• Exposure to RBCL and hemorrhagic CSF activated inflammatory pathways in fetal astrocytes and brain microvascular endothelial cells.
• Interleukin-1B (IL1B) was significantly upregulated following exposure to RBCL and hemorrhagic CSF.
• IL1B demonstrated a partially protective effect on neurogenesis when its receptor was antagonized.

Conclusions:

• The SVZ-on-a-chip model is effective for studying IVH pathology and neuroinflammation.
• IL1B plays a significant role in regulating neurogenesis during IVH.
• IL1B represents a potential therapeutic target for mitigating neurodevelopmental deficits in preterm infants with IVH.