# IGF-1 and Innate Immunity in Neonatal Brain Injury

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $440,066

## Abstract

Abstract
Neonatal Intraventricular hemorrhage (IVH) originates from the underdeveloped germinal matrix, a site of cell
rapid cell division adjacent to the lateral ventricles of the brain. IVH leads to brain injury and life-long neurological
disability. Within the same time frame that neonatal IVH occurs, the brain is rapidly producing the cells needed
for myelination. Oligodendrocytes, the myelin-forming cells of the brain, are derived from oligodendrocyte
progenitor cells (OPCs). OPCs are fragile cells - exquisitely sensitive to many factors present across multiple
neurological diseases such as excitotoxicity, inflammatory cytokines, and oxidative stress. Across a wide
spectrum of neurological diseases, neuroinflammation disturbs OPC development. IVH both causes
inflammation and leads to white matter pathology. Microglia, the endogenous macrophages of the brain, are the
main effectors of neonatal neuroinflammation and are implicated in many forms of neonatal brain injury.
However, microglia also produce insulin-like growth factor-1 (IGF-1), which is required for normal OPC
development.
IGF-1 is decreased by other forms of neonatal brain injury but has not been studied in IVH. Our preliminary data
indicates that microglia increase production of inflammatory cytokines and reduce IGF-1 production after
exposure to hemoglobin. Both of these effects could impair OPC development. Supplementing IGF-1 after IVH
may be a powerful therapy because IGF-1 not only supports OPC health, but also modulates inflammation and
reduces production of cytokines that are harmful to OPCs. These dual roles of IGF-1: supporting OPC
development and altering the phenotype of immune cells (including microglia), makes it an excellent candidate
for treating IVH in which both inflammation and white matter pathology occur. This project is designed to better
understand how microglia respond to IVH, with a focus on how hemoglobin and IGF-1 affect inflammation and
OPC development. It is also designed to trace OPC fate after IVH and determine if myelination failure is due to
OPC loss versus maturation failure. We will trial IGF-1 as a therapy for IVH, and test its ability to modulate
microglial activation and improve myelination.

## Key facts

- **NIH application ID:** 10980077
- **Project number:** 1R01NS134626-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** BRANDON A MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $440,066
- **Award type:** 1
- **Project period:** 2024-09-18 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980077

## Citation

> US National Institutes of Health, RePORTER application 10980077, IGF-1 and Innate Immunity in Neonatal Brain Injury (1R01NS134626-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10980077. Licensed CC0.

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