# Disease Mechanisms of Prenatal and Pediatric Acquired Hydrocephalus

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2021 · $352,188

## Abstract

Abstract
Infections, both bacterial and viral, have been linked to pediatric hydrocephalus and can impact the nascent
brain’s developmental programs. In fetal development, stem cells line the ventricles and provide neurons and
glia required for brain development; ventricle-contacting stem cells also generate a protective epithelial
monolayer of ependymal cells. As ependymal cells form a barrier wall along the ventricles, the remaining stem
cells are relegated to the subependymal zone and retain only a thin apical process in contact with the cerebral
spinal fluid. This unique arrangement characterizes the stem cell niche along the lateral walls of the lateral
ventricle and supports continued neurogenesis in postnatal development. It is known that certain viruses
preferentially target the ependymal cell lining of the ventricles resulting in loss of the structural support and barrier
functions provided by the ependymal cells. Infection during periods of ependymogenesis and neurogenesis
would critically impact the development and function of the stem cell niche.
The premise of this proposal is to model infection in a controlled manner and characterize damage to, and
reparative mechanisms of, the ventricular-subventricular zone stem cell niche over the course of post-infectious
hydrocephalus. Previous work mapped the lateral ventricles in 3D (mouse and human) to determine volume,
surface area and curvature changes over the course of development. New data from lineage tracing (multi-color
vectors) and live cell imaging will document stem cell-mediated ependymogenesis versus neurogenesis and
address stem cell depletion in normal development (Aim 1). The hypothesis that enlarged ventricles
(hydrocephalus) impact stem cell niche functions and compromise neurogenesis will first be tested using a
neurovirulent component of influenza, neuraminidase, which is known to cause hydrocephalus in mice (Aim 2).
After intraventricular injection of neuraminidase in embryonic and postnatal mice, sequelae of post-infectious
hydrocephalus, critical developmental time points and potential for stem cell-mediated repair will be examined.
Following examination of a univariant, neuraminidase, hydrocephalus model, bona fide post-infectious
hydrocephalus using a mouse variant of influenza will be modeled (Aim 3). Intraventricular, intraplacental and
intranasal routes will be assessed and the impact on the ventricular-subventricular stem cell niche and its
functions will be examined. The hypothesis that induction and severity of influenza-induced post-infectious
hydrocephalus can be mitigated by prior homologous or heterologous immunity will also be tested. These studies
will define the impact that post-infectious hydrocephalus has on a critical stem cell niche and its capacity for
regenerative repair – guiding treatment strategies for post-infectious hydrocephalus.

## Key facts

- **NIH application ID:** 10094263
- **Project number:** 5R01NS110586-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** JOANNE C CONOVER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $352,188
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10094263

## Citation

> US National Institutes of Health, RePORTER application 10094263, Disease Mechanisms of Prenatal and Pediatric Acquired Hydrocephalus (5R01NS110586-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10094263. Licensed CC0.

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