# Oligodendrocyte Progenitor Cell Response to White Matter Stroke

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $14,409

## Abstract

Project Summary/Abstract
White matter stroke is a progressive vascular disease that leads to neurological deficits and can cause dementia.
It produces an area of cell death and axonal disruption (the “infarct”) and induces a response of reactive
astrocytes and oligodendrocyte precursors cells. In 70% of clinical studies, white matter strokes expand from
preexisting lesions into adjacent white matter (the “peri-infarct” region) further damaging and disrupting neuronal
connections, causing substantial disability. Currently, what is largely known about white matter repair is derived
from studies in non-stroke injuries of white matter such as multiple sclerosis (MS). Limited remyelination occurs
in MS through an oligodendrocyte progenitor cell (OPC) response in which OPCs proliferate, differentiate into
oligodendrocytes, and remyelinate axons. OPCs proliferate in the peri-infarct region in white matter stroke, but
unlike in MS, they do not appear to mature into myelinating oligodendrocytes. This study will utilize a recently
developed mouse model of diffuse white matter stroke that produces progressive damage from the small blood
vessels in the corpus callosum. This model produces a larger lesion and more closely mimics advanced, chronic
stages of human white matter stroke. In aim 1, I will map the OPC response and myelination events after white
matter stroke and determine cell fate outcomes of OPCs using novel viral and transgenic approaches. In aim 2,
I will determine the role of OPC differentiation induced by candidate genes in white matter repair in vivo. These
genes were identified to be highly altered in stroke-induced OPCs as well as to promote OPC differentiation in
vitro. The outcome of this work will be to identify novel molecular targets for neural repair and functional recovery
in white matter stroke.

## Key facts

- **NIH application ID:** 10599265
- **Project number:** 5F31NS118904-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Natalie Melinda Shih
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $14,409
- **Award type:** 5
- **Project period:** 2021-05-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599265

## Citation

> US National Institutes of Health, RePORTER application 10599265, Oligodendrocyte Progenitor Cell Response to White Matter Stroke (5F31NS118904-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10599265. Licensed CC0.

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