# lncRNAs and Anesthetic-Induced Developmental Neurotoxicity

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $217,046

## Abstract

PROJECT SUMMARY
In 2016, the U.S. Food and Drug Administration warned that repeated or lengthy use of general anesthetics in
children below the age of three might affect their brain development. This warning raises serious concerns
regarding the safety of pediatric anesthesia. There are two main barriers in the research field of anesthetic-
induced developmental neurotoxicity (AIDN): 1) So far, most of the evidence for AIDN was obtained from
animal studies. The results from human studies remain inconclusive. 2) The mechanisms are largely unknown.
The goal of this study is to address both of these barriers by using an in vitro system of three-dimensional (3D)
human mini brains generated from induced pluripotent stem cells and mouse models to study novel
mechanisms of long non-coding RNAs (lncRNAs). Human mini brains are more similar to developing human
brains, both structurally and functionally, than the widely used 2D neurons. Our preliminary data provided the
first evidence showing that clinically relevant doses of propofol and sevoflurane, two commonly used pediatric
anesthetics, induced acute cell death in human mini brains. We also found that neonatal propofol exposure
altered lncRNA expression profiles and caused multiple adverse effects in mice (E/I imbalance, neuronal death,
and impaired memory function). Our exciting findings suggest that the abnormally expressed lncRNAs might
contribute to AIDN. Thus, we will examine the role and mechanism of lncRNAs in AIDN such as abnormal
neuronal activity and networks using both human mini brain and mouse models. The HyperCAM Alpha
equipment would significantly improve our productivity and capacity by enabling high throughput, detailed data
collection of our electrophysiological studies on 3D human mini brains and mouse tissue slices. This proposal
is expected to provide new molecular and electrophysiological mechanistic insights into the
neurodevelopmental consequences of pediatric anesthetic exposure. This will further aid in the development of
more rational neuroprotective strategies related to pediatric anesthetic use, and movement towards a better
assurance of safety for pediatric anesthesia use.

## Key facts

- **NIH application ID:** 10382813
- **Project number:** 3R01GM112696-08S1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Xiaowen Bai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $217,046
- **Award type:** 3
- **Project period:** 2014-05-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10382813

## Citation

> US National Institutes of Health, RePORTER application 10382813, lncRNAs and Anesthetic-Induced Developmental Neurotoxicity (3R01GM112696-08S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10382813. Licensed CC0.

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