# Myo-inositol regulation of myelination in development and hypoxic newborn brain injury

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $70,146

## Abstract

Abstract
Diffuse white matter damage, a type of brain injury, commonly occurs with premature birth and is a leading
cause of cerebral palsy and neurodevelopmental disorders. This type of brain injury is often caused by hypoxia
due to immature lung development. Accumulating evidence from both postmortem human tissue and rodent
models suggests delay of glial maturation is a major underlying cause of hypoxia-induced structural and
functional neurological abnormalities. In particular, neonatal hypoxia causes delayed maturation of
oligodendrocytes, the myelin-forming glia of the central nervous system (CNS), and results in myelin defects
and motor and cognitive abnormalities. Human infants typically undergo extensive glial maturation and
myelination during late prenatal and early postnatal life, when nutrition can be supplied solely by the mother.
We have an incomplete understanding of maternally-derived factors that contribute to normal CNS myelination
and which could be safely administered to infants to promote recovery from white matter injury. The goal of
this research is to understand the role of the natural sugar alcohol myo-inositol in regulating signaling
pathways that are essential for normal developmental myelination, and to determine whether supplementation
of myo-inositol can promote recovery from white matter injury caused by chronic neonatal hypoxia. The
central hypothesis is that myo-inositol activates phosphoinositide signaling pathways that promote
oligodendrocyte myelination during development and in white matter injury. We will test this hypothesis in
gain- and loss-of-function studies using in vitro and in vivo rodent models of normal development and chronic
neonatal hypoxia. Aim 1 will test whether oligodendrocyte uptake of myo-inositol drives myelin wrapping during
development by modulating oligodendrocyte phosphoinositide levels. Aim 2 will test whether myo-inositol
rescues myelin defects and promotes functional recovery in chronic neonatal hypoxia by acting directly on
oligodendrocytes. Upon completion these studies will have important implications both for understanding basic
oligodendrocyte biology as well as for potential therapeutics for neonatal white matter injury. In order to
conduct these studies, I will learn electron microscopy, mass spectrometry, and CRISPR-based gene editing
under the guidance of my sponsor, Dr. Chan. I will also receive further training in critical career development
skills such as presentations, scientific writing, and grantsmanship from Dr. Chan and by participating in UCSF
seminars. I am confident that completion of the research goals described here, the mentorship I receive from
Dr. Chan, and the rigorous research environment at UCSF will enable me to achieve my long-term goal of
becoming a tenure-track independent investigator in academia.

## Key facts

- **NIH application ID:** 9920596
- **Project number:** 5F32HD098829-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** SARAH E RAISSI
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,146
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920596

## Citation

> US National Institutes of Health, RePORTER application 9920596, Myo-inositol regulation of myelination in development and hypoxic newborn brain injury (5F32HD098829-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9920596. Licensed CC0.

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