Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage

Hydrocephalus remains one of the most common neurosurgical disorders worldwide and is currently treated primarily with surgical diversion of CSF using implanted shunts. Although lifesaving, shunts frequently fail, require repeated surgeries, and do not directly address the underlying biological injury occurring within the brain and ventricular system. Many patients continue to experience lifelong neurological complications despite surgical treatment. This project has the potential to shift hydrocephalus treatment from surgical management toward mechanism-guided prevention. By targeting ventricular inflammation early after hemorrhage, the investigators aim to prevent the biological processes that drive excessive CSF accumulation, ventricular remodeling, ependymal injury, and chronic inflammatory scarring. Successful completion of this work could establish the first pharmacologic strategy designed to prevent hydrocephalus rather than simply treat its consequences after it develops.

The impact of this approach could extend far beyond adult hemorrhage-related hydrocephalus. Similar inflammatory mechanisms are believed to contribute to hydrocephalus caused by prematurity, infection, and traumatic brain injury. In particular, post-infectious and neonatal hydrocephalus remain major causes of childhood disability and death in many low-resource regions where access to shunt surgery and specialized neurosurgical care is limited. A scalable medical therapy capable of reducing hydrocephalus progression could therefore have a substantial global health impact. In addition, this project establishes a new translational framework for studying the ventricular neuroimmune microenvironment through real-time analyses of CSF biomarkers and extracellular vesicles. These tools may ultimately enable personalized monitoring and targeted treatment approaches for multiple forms of hydrocephalus and related neuroinflammatory disorders.

Inclusion criteria

• Age ≥18 years
• Diagnosis of aneurysmal subarachnoid hemorrhage (aSAH)
• Hunt Hess grade IV to V
• Radiographic evidence of intraventricular hemorrhage (IVH)
• Clinically indicated EVD placement as part of standard neurocritical care
• Ability to enroll during the acute post-hemorrhagic inflammatory period, ideally within 24 hours of EVD placement

Exclusion criteria

• Pre-existing ventriculoperitoneal shunt dependence
• Severe baseline immunosuppression
• Uncontrolled systemic infection unrelated to hemorrhage
• Pregnancy
• Anticipated withdrawal of life-sustaining therapy within 24 hours
• Inability to safely receive investigational ventricular therapy