Exploring and translating novel approaches targeting the choroid plexus for the treatment of hydrocephalus: a literature review

Hydrocephalus is common with a mixed phenotype and aetiology. Its treatment is predominantly surgical, with temporary or permanent cerebrospinal fluid (CSF) diversion, which does not address the underlying disease mechanism. The choroid plexus (ChP), a secretory epithelium found in all four ventricles of the brain, produces most CSF within the central nervous system and has been investigated extensively over the past century to understand its function and potential role as a therapeutic target. Past attempts at either medically or surgically controlling its rate of secretion have not significantly altered our approach to the treatment of hydrocephalus, with CSF diversion remaining the main intervention. Rodent models of post-haemorrhagic hydrocephalus (PHH) have advanced our understanding of choroid plexus function in health and disease. Pre-clinical experiments have demonstrated a hypersecretory response in the ChP that may contribute to PHH. Targeting the choroid plexus directly may therefore present a novel therapeutic method. These findings have led to a significant increase in pre-clinical studies exploring this hypersecretory response and how to modulate it. Translating these promising results to clinical practice will rely on the development of large animal hydrocephalus models, which thus far has been limited. This literature review discusses the recent advances in targeting the ChP as a treatment for hydrocephalus, both surgically and non-surgically, and the current barriers to further advancement of this approach.