# Corticospinal Tract Development in Intrauterine Growth Restriction

> **NIH NIH K08** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2021 · $163,080

## Abstract

Project Summary
 Infants born following intrauterine growth restriction (IUGR) are at risk for the development of cerebral
palsy (CP). However, it is not precisely understood how perinatal neurologic injury due to IUGR results in
motor dysfunction. Using a novel thromboxane A2 (TXA2) murine model of IUGR, we have previously
demonstrated significant downregulation of major myelin genes (MoBP, PLP1, CNPase, MOG) in whole brain,
decreased corticospinal tract (CST) volume in the brain, and impaired gait. The most profound injury occurred
when IUGR was combined with postnatal hyperoxia exposure, suggesting a “double hit” mechanism. These
findings support a model in which transcriptional changes occur after IUGR that alter oligodendrocytes (OL)
making them more susceptible to hyperoxia. Our findings lead us to the central hypothesis that IUGR with
postnatal hyperoxia results in cell specific changes to the OL transcriptome that lead to pathologic changes to
the CST and motor deficits seen in CP. In Aim 1, in vivo genetic and biochemical methods will be employed in
this model to determine how IUGR/postnatal hyperoxia change the OL transcriptome. This aim will add further
understanding to the underlying causes of white matter (WM) injury after IUGR. As CST is known to be
disturbed in spastic CP, the most common type of CP in perinatal brain injury, Aim 2 will evaluate CST
development using advanced in vivo imaging techniques to demonstrate how IUGR/postnatal hyperoxia alter
development of descending motor tracts in the spinal cord. In Aim 3, altered motor input resulting in distal limb
movement abnormalities and increased hyperreflexia/ spasms will be quantified using novel motor tests. The
innovative motor testing employed in this aim will provide the means to rigorously quantify motor dysfunction
resulting from our injury model and compare it to motor dysfunction seen in CP.
 This study will impact the field by 1) providing insight into specific changes to the OL transcriptome
leading to abnormal myelination and CST development and 2) expanding the understanding of the
development of the CP phenotype in IUGR. This study is significant because of its quantitative approach to
imaging modalities and motor assessments that can be applied more broadly to other murine models of
perinatal brain injury and provide a basis for investigating novel therapeutic interventions in humans. Finally,
this study will provide an excellent vehicle for the applicant to develop into an independent investigator.
Investigations will be performed in an environment with an established history of successful mentorship of
junior faculty to independence. With the support of this application, the applicant will 1) advance her technical
skills (RiboTag RNA isolation, next generation sequencing, murine MRI, electromyography and kinematic
testing techniques) and 2) learn advanced biostatistics. Future independent studies will focus on the interplay
between pathways altered by IUGR/hype...

## Key facts

- **NIH application ID:** 10136658
- **Project number:** 5K08HD102023-02
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Jill Chang
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $163,080
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136658

## Citation

> US National Institutes of Health, RePORTER application 10136658, Corticospinal Tract Development in Intrauterine Growth Restriction (5K08HD102023-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136658. Licensed CC0.

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