# The Role of Complement in Cerebrospinal Fluid Shunt Infections

> **NIH NIH K08** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $192,132

## Abstract

PROJECT SUMMARY
Cerebrospinal fluid shunt infections are a frequent and serious complication of the treatment of hydrocephalus,
occurring in 5-30% of patients1, 2. These infections are associated with significant long-term neurologic
sequelae such as lower IQ, poor school performance and increased risk of seizures 9-13. The mechanisms
responsible for the severe neurologic damage associated with shunt infection are unknown.
Studies have demonstrated the role of complement in normal neurologic development through developmentally
appropriate complement mediated synaptic pruning by microglia 19,20,22. Additional studies have revealed the
role of complement in a variety of neurologic disorders and infection supporting a central role for complement
in central nervous system homeostasis and pathology24-33. My preliminary studies in an animal model of shunt
infection have demonstrated elevated levels of the complement components C3 and C5 in brain tissue at day 5
and 10 when bacterial burdens are low, suggesting complement may mediate the neurologic damage
associated with shunt infections. This is further supported by my preliminary data demonstrating that synaptic
pruning is less dramatic in C3 knockout mice. The overall objective of this proposal is to understand the role of
complement in a murine model of CNS catheter infection, to facilitate the future identification of novel
therapeutic targets to limit neurologic damage in pediatric patients. Understanding the mechanisms
whereby complement mediates neurologic damage would allow us to take advantage of many
complement inhibitors that are being developed for clinical medicine as potential adjuvants to
antibiotic therapy to improve long-term patient outcomes 35,36.
Our central hypothesis is that complement components induce microglial-mediated synaptic pruning and are
responsible for late-stage cerebral edema. To test this hypothesis, we will perform experiments outlined in two
specific aims. In Aim 1, we will identify the primary mode of complement pathway activation during CNS S.
epidermidis catheter-associated infection and functional importance. In Aim 2, we will define the molecular
mechanisms of complement-mediated damage during CNS catheter infection.
Finally, the candidate is a pediatric infectious disease specialist with a long-standing experience investigating
shunt infections. She is a well-supported candidate with the goal of becoming a physician scientist and would
highly benefit from a Clinical Scientist Development Award.

## Key facts

- **NIH application ID:** 10147925
- **Project number:** 5K08NS110923-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Gwenn L Skar
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $192,132
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147925

## Citation

> US National Institutes of Health, RePORTER application 10147925, The Role of Complement in Cerebrospinal Fluid Shunt Infections (5K08NS110923-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10147925. Licensed CC0.

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