# Mechanisms of White Matter Repair in Subcortical White Matter Ischemia

> **NIH NIH R37** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $390,000

## Abstract

Project Summary/Abstract
White matter ischemia is a progressive vascular disease that leads to focal neurological deficits, accumulates to
cause dementia, and accelerates the pathology of Alzheimer's Disease. The term white matter ischemia or white
matter hyperintensity, based on imaging, corresponds to several disease pathologies, including progressive
blood brain barrier breakdown, small focal strokes and end-arterial hypoperfusion. White matter ischemia is
strongly age-associated: at age 80 all of us will have white matter hyperintensities on MRI. Despite substantial
pre-clinical study of mechanisms of white matter repair in inflammatory white matter disease (such as multiple
sclerosis), there is little information on how cerebral white matter responds to white matter ischemia, and may
initiate neural repair. This grant utilizes a model of white matter ischemia in the mouse, which produces diffuse
and progressive damage from the small vessels in the subcortical white matter, to determine the mechanisms of
white matter repair. The studies characterize candidate molecular systems that mediate this process and identify
neuronal network function in white matter ischemia and during repair and recovery. The studies will determine
the effects of age on these processes. This grant will use an innovative platform of technologies, including a
newly developed mouse model, transgenic cellular fate-mapping, optogenetic and resting state MRI studies, and
viral gain and loss of function approaches. The outcome of this work will be to identify novel molecular targets
for neural repair in white matter ischemia, develop an understanding of the neuronal network function that leads
to behavioral deficits in this disease, and develop an imaging biomarker for repair and recovery in white matter
ischemia.

## Key facts

- **NIH application ID:** 10123016
- **Project number:** 5R37NS102185-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Stanley Thomas Carmichael
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123016

## Citation

> US National Institutes of Health, RePORTER application 10123016, Mechanisms of White Matter Repair in Subcortical White Matter Ischemia (5R37NS102185-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10123016. Licensed CC0.

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