# Tau/pTau as Biomarkers of Anesthesia/Surgery-Associated Neurocognitive Outcomes in Children

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $260,007

## Abstract

Project Summary/Abstract.
 Each year, millions of children in the United States have surgery under anesthesia. Recent population
studies have suggested that children who undergo multiple exposures to anesthesia and surgery at an earlier
age could have an increased risk for developing neurocognitive impairment. It is therefore urgent to perform
studies in this new and still under-investigated area: anesthesia/surgery-associated neurocognitive impairment
in children. Thus far, no biomarker for identifying neurocognitive impairment currently exists and this gap in
knowledge impedes the progress of the research. To address this issue, we have made a proposal to establish
the biomarker for anesthesia/surgery-associated neurocognitive impairment in children. Consistent with the
notion that Tau protein is a marker of brain injury in infants and children with hypoxic ischemic encephalopathy
and hydrocephalus, our preliminary studies showed that multiple exposures to the anesthetic sevoflurane
increased blood Tau levels and induced neurocognitive impairment in young mice. Thus, the hypothesis of the
proposed study is that children have elevated Tau and phosphorylated Tau levels and develop neurocognitive
impairment after multiple, but not single, surgeries under anesthesia. We will test this hypothesis in two cohorts
of children between 3 and 5 year-old: (1) 20 children undergoing reconstruction surgery to repair burn scars
who will likely develop the neurocognitive impairment due to the histories of multiple exposures to
anesthesia/surgery used to treat the burn; and (2) 20 children having hernia repair surgery for the first time
who will likely NOT develop the neurocognitive impairment due to a lack of history of exposure to
anesthesia/surgery. In Aim 1, we will use the NIH Toolbox and innovative nanobeam technology to determine
neurocognitive outcomes as well as blood Tau and phosphorylated Tau levels before and after the
anesthesia/surgery. We will also collect information of eligible:recruit ratio, retention rates, protocol safety, and
power calculation. In Aim 2, we will measure Tau and phosphorylated Tau in urine, feces and saliva of 10
participants recruited in Aim 1. Taken together, these high risk but high impact prospective cohort studies in
children would provide important information for the application of the R01 grant to further establish Tau or
phosphorylated Tau as the biomarker of the anesthesia/surgery-associated neurocognitive impairment in
children. The establishment of the biomarker will help diagnose the anesthesia/surgery-associated
neurocognitive impairment, identify neurotoxic anesthetics, and determine the outcomes of intervention(s).
These research works will ultimately lead to safer anesthesia/surgery care and better postoperative outcomes
for children. Therefore, these efforts are consistent with the goal of the funding opportunity announcement
PAR-18-214: to improve the safety and effectiveness of current drugs for pediatric...

## Key facts

- **NIH application ID:** 9917802
- **Project number:** 5R21HD098754-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Zhongcong Xie
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $260,007
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917802

## Citation

> US National Institutes of Health, RePORTER application 9917802, Tau/pTau as Biomarkers of Anesthesia/Surgery-Associated Neurocognitive Outcomes in Children (5R21HD098754-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9917802. Licensed CC0.

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