Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage

Plain-language summary

Hydrocephalus is a serious condition in which fluid builds up inside the brain, often requiring lifelong surgical placement of a shunt to drain excess cerebrospinal fluid (CSF). One of the most common causes of hydrocephalus is bleeding into the brain's fluid spaces after aneurysm rupture, prematurity, or infection. Currently, no medication exists to prevent hydrocephalus from developing after these injuries. The investigators' recent research suggests that hydrocephalus may result not only from blocked fluid pathways but also from harmful inflammation within the brain's ventricular system. The investigators discovered that inflammation activates the choroid plexus, the tissue that produces CSF, causing excessive CSF production and inflammatory injury to the ventricular lining and surrounding brain tissue. The investigators also identified inflammatory biomarkers and extracellular vesicles in human CSF that may enable real-time monitoring of these disease processes. In this project, the investigators will perform a first-in-human pilot study testing whether targeted "intraventricular mTOR inhibition" can reduce ventricular inflammation and prevent hydrocephalus after severe brain hemorrhage. The medication will be delivered via temporary ventricular drains already in place as part of routine clinical care. The investigators will study safety, inflammation, CSF production, brain imaging changes, and whether patients ultimately require permanent shunts. Although this initial study focuses on adults with hemorrhage-related hydrocephalus, our long-term goal is to develop non-surgical therapies that could help children with hydrocephalus caused by prematurity or infection, especially in regions where access to neurosurgical care and shunt surgery is limited.

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