Choroid plexus remodeling associated with inflammatory CSF exposure in preterm acquired hydrocephalus

Acquired hydrocephalus in preterm infants follows intraventricular hemorrhage (IVH) or central nervous system infection and is associated with inflammatory cerebrospinal fluid (CSF) profiles. We integrated clinical magnetic resonance imaging (MRI), CSF cytokine profiling, primary human choroid plexus (ChP) epithelial and endothelial cell assays, and independent transcriptomic and proteomic datasets to investigate ChP remodeling. Infants requiring CSF diversion exhibited greater ChP thickness independent of gestational age, ventricular size, and IVH severity, supporting its potential as a biomarker. Growth factor-enriched inflammatory CSF increased proliferation in primary human ChP epithelial and endothelial cells; EGFR and VEGFR inhibition attenuated these responses, and recombinant epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) reproduced proliferative effects. Independent IVH transcriptomic data confirmed Mki67 elevation in IVH ChP tissue. Integrated proteomic trajectories support a temporally dynamic remodeling framework linking acute inflammatory signaling to proliferative ChP activation and structural remodeling.