# The role of metabolic and hemodynamic reserve in age-related brain vulnerability in pediatric sickle cell anemia

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $545,352

## Abstract

PROJECT ABSTRACT
If oxygen supply to the brain does not match its demands, cellular functions are impeded and
can lead to cell death. A margin is created between oxygen supply and brain demand by
metabolic and hemodynamic reserves. Our preliminary data show that children may have less
reserve due to the critical, but costly energy demands of brain growth and maturation. We have
shown that lower oxygen supply (hypoxemia) also decreases reserves, and during childhood,
may result in impaired brain growth and development. Children with sickle cell anemia (SCA)
have chronic hypoxemia due to reduced hemoglobin. Children with SCA have smaller brain
volumes and decreased cortical thickness than unaffected children. The intersection of
hypoxemia and brain development is poorly understood, impeding our ability to optimize brain
development and neurologic outcomes in children with hypoxemia. The goal of this project is to
identify physiologic mechanisms of vulnerability and age-dependent consequences of
hypoxemia. Our central hypothesis is that the high cerebral metabolic demand in younger
children decreases oxygen reserve, resulting in an age-dependent increased risk for impaired
brain growth in children with lower oxygen supply. First, we will assess normal developmental
changes in metabolic and hemodynamic reserve in 80 healthy children ages 4-21 to determine
age-dependence of reserves (Aim 1). Next, we will determine the effects of hypoxemia on
metabolic and hemodynamic reserves and the consequence of hypoxemia on brain
development. We will compare 40 children with SCA and 40 age and sex-matched controls at
baseline and 3 year follow-up imaging, and examine cortical thickness changes in the two
cohorts (Aim 2). Finally, we will evaluate whether oxygen reserve increased through
hydroxyurea treatment in an SCA cohort impacts long-term brain development. We will utilize a
large sickle cell database with 16 years of brain imaging to compare cortical thickness
maturation and total brain volumes between treated and untreated children (Aim 3). Determining
the age-dependence of hypoxemic vulnerability and its effect on brain development will allow us
to personalize treatment strategies for children at high risk for neurodevelopmental injury to be
more aggressive during periods of highest vulnerability.

## Key facts

- **NIH application ID:** 10179982
- **Project number:** 1R01NS121065-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Kristin Guilliams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $545,352
- **Award type:** 1
- **Project period:** 2021-06-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179982

## Citation

> US National Institutes of Health, RePORTER application 10179982, The role of metabolic and hemodynamic reserve in age-related brain vulnerability in pediatric sickle cell anemia (1R01NS121065-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10179982. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*