# Astrocyte functions in neonatal brain

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $332,500

## Abstract

PROJECT SUMMARY
The neonatal brain is very vulnerable to compromises in its blood supply. Cerebral vascular dysfunction is an
important component in the development of neonatal brain injury. Neonatal cerebrovascular disease caused
by oxidative stress during seizures, hypoxia/asphyxia, and ischemia frequently leads to lifelong neurological
complications in babies. Maintaining astrocyte functionality is a key component in neuroprotection via
cerebral blood flow regulation, blood-brain barrier (BBB) integrity, and glutamate clearance from the brain
extracellular space. The project is focused on novel endogenous mechanisms that promote astrocyte survival
during oxidative stress caused by seizures and glutamate excitotoxicity in the neonatal brain. Our preliminary
data in newborn piglet brain suggest that hydrogen sulfide (H2S), a gasotransmitter produced by cortical
astrocytes or released from the donor molecules, exhibits antioxidant and antiapopototic properties. We
hypothesize that H2S preserves astrocyte functions during glutamate excitotoxicity in the neonatal brain.
We will test three specific hypotheses using intact newborn pigs and freshly isolated and cultured astrocytes:
1) Astrocyte H2S production is activated during oxidative stress; 2) H2S protects astrocytes against
excitotoxicity via mitochondrial targeting and mTORC1 signaling; 3) H2S preserves astrocyte functionality
during neonatal seizures and glutamate excitotoxicity.
We will use an exceptional combination of complementary techniques in a large animal model that allows in
vivo and in vitro investigation of newborn circulation. Such research is unique, as it combines functional and
mechanistic studies in intact cerebral circulation with investigation of the cellular and molecular defense
mechanisms counteracting astrocyte injury. Gene silencing and pharmacological approaches will be used to
pinpoint causative relationships among H2S, glutamate excitotoxicity, oxidative stress, and astrocyte functions.
The project will lead to the development of novel translationally relevant treatments to provide
neuroprotection to the neonatal brain during seizures. Importantly, we have collected sufficient preliminary
data to demonstrate the feasibility of our proposal and to support our hypothesis on critical role of H2S in
astrocyte survival during oxidative stress in the neonatal brain.

## Key facts

- **NIH application ID:** 9954171
- **Project number:** 5R01NS101717-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Helena Parfenova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $332,500
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954171

## Citation

> US National Institutes of Health, RePORTER application 9954171, Astrocyte functions in neonatal brain (5R01NS101717-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9954171. Licensed CC0.

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