Molecular hallmarks of hydrocephalus

Hydrocephalus (HC) is a failure of brain and cerebrospinal fluid (CSF) homeostasis often associated with dilation of the CSF-filled ventricles (ventriculomegaly). Hallmarks of HC include aberrant CSF dynamics, neural stem cell dysfunction resulting in impaired neurogenesis and corticogenesis, biomechanical instability at the brain-CSF interface, and disrupted synaptogenesis and neural circuitry. Pleiotropic mechanisms, including genetic and environmental insults to the brain, contribute to neurodevelopmental comorbidities. Hypothesis generation from genome-wide, single-cell multi-omic analyses coupled to experimental validation using induced pluripotent stem cell-derived cerebral organoids will refine molecular classification of HC subtypes and may lead to precision-based surgical and pharmacologic treatments.