# Investigating the cellular mechanisms leading to repetitive shunt failure in the treatment of pediatric hydrocephalus

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $474,352

## Abstract

PROJECT SUMMARY
 Hydrocephalus, an imbalance between cerebrospinal fluid production and absorption, is diagnosed in
more than 1 in 500 people in the United States. Approximately 80% of these patients will suffer long-term
neurological deficits. Genetic diseases, meningitis, subarachnoid hemorrhage, stroke, traumatic brain injury, or
tumors cause hydrocephalus. The common treatment for all hydrocephalus patients is CSF drainage by
shunting. Despite all our efforts, shunts still have the highest failure rate of any neurological device. A
shocking 98% of shunts fail after just ten years, a rate bumped up by the 80% of patients who suffer from tens
if not hundreds of repetitive shunt failures.
 Shunts fail after becoming obstructed with attaching glia, creating a substrate for more glia or other
cells and tissues (e.g. choroid plexus) to secondarily bind and block the flow of CSF through the shunt. Since
glial attachment is a primary mechanism for shunt failure, we need to find out what it is about the
pathophysiology of hydrocephalus that cause glia to attach and cause repetitive shunt failure. Until these cues
are identified, we cannot address shunt failure in a principled way.
 In our first approach, we correlate patient revision history to change in cell attachment, hypothesizing
that shunt failure exacerbates the likelihood for repeat shunt failure. In our second approach, we probe the
mechanisms of shunt failure due to ever-present glia, specifically, how glial attachment changes as a function
of factors influenced by repeat shunt failure. In our third approach, we probe mechanisms of shunt failure by
blocking factors influenced by repeat shunt failure, and in doing so, propose methods to mitigate perpetual
shunt failure. Methods include a first application of high-throughput, high-resolution, multi-spectral imaging and
use of the FARSIGHT toolkit to provide a comprehensive quantitative analysis of the interaction between glia
and the shunt.
 This project will set the stage for specific cause-effect engineering hypotheses to improve shunt design
and ultimately lead to a fundamental leap of knowledge in hydrocephalus treatment. It will provide the
foundation for my independent career managing a successful bioengineering research laboratory improving
neuroprosthetics using biologically inspired design principles while providing professional development
opportunities that allow me to train with the fields leading experts.

## Key facts

- **NIH application ID:** 9935125
- **Project number:** 5R01NS094570-05
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Carolyn A Harris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $474,352
- **Award type:** 5
- **Project period:** 2016-06-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935125

## Citation

> US National Institutes of Health, RePORTER application 9935125, Investigating the cellular mechanisms leading to repetitive shunt failure in the treatment of pediatric hydrocephalus (5R01NS094570-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9935125. Licensed CC0.

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