187 Uncovering Dynamic CSF Proteomic Signatures in Post-Hemorrhagic Hydrocephalus

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INTRODUCTION: Post-hemorrhagic hydrocephalus (PHH) is a common complication of germinal matrix hemorrhage in premature infants and a leading cause of neonatal hydrocephalus. Defining the inflammatory mechanisms underlying PHH pathogenesis and progression may provide guidance for treatment strategies, including cerebrospinal fluid (CSF) diversion. Prior biomarker studies have been biased towards limited sets of pre-selected cytokines. Moreover, the temporal evolution of inflammatory biomarkers in PHH has not been systematically explored. We hypothesize that high-sensitivity, unbiased proteomic profiling of CSF offers a means to identify PHH-specific immune signatures and monitor longitudinal changes. METHODS: CSF samples from 29 pediatric patients (PHH n=9, NMDARE n=5, brain tumor n=10, control n=5) were analyzed using the Olink® Explore 384 inflammation I and II panels (736 immune-related proteins; 641 retained after quality control). Differentially abundant proteins (DAPs) were identified for pathway enrichment (Reactome 2024) and protein-protein interaction network analyses. RESULTS: PHH revealed 539 DAPs enriched in alternative complement activation, coagulation, and platelet degranulation pathways. NMDARE showed 71 DAPs enriched in IL-10 and IL-18 signaling pathways. There were no statistically significant DAPs for brain tumor patients. Kinase co-expression analysis exhibited RIPK2 dominance in PHH and PIM2 in NMDARE. Longitudinal analysis in PHH demonstrated downregulation of inflammatory proteins over time and emerging TNF superfamily signaling. Notably, NELL2 was consistently downregulated in PHH compared to all other CNS diseases. CONCLUSIONS: PHH is marked by a unique and evolving neuroinflammatory profile, characterized by early innate immune activation and later adaptive signaling. These findings identify biomarkers and therapeutic targets—including RIPK2 pathway components and NELL2—that may inform future clinical strategies for PHH.

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