# Glial cell line-derived neurotropic factor and postoperative cognitive impairment in young rats

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $328,410

## Abstract

Millions of children each year undergo anesthesia and surgery in the U.S.A. Recent studies
suggest that anesthesia and surgery can cause cognitive impairment in the developing brain. This
finding causes significant concern. To be able to identify children that may be at risk for developing
cognitive dysfunction and to provide intervention to those selective children, it is necessary to have
biomarkers for surgery-induced cognitive dysfunction. Our preliminary study showed that surgery on
postnatal day 7 (P7) rats impaired their learning and memory. Surgery also decreased glial cell line-
derived neurotropic factor (GDNF) in the brain and urine. Intracerebroventricular injection of GDNF
attenuated surgery-induced learning and memory impairment. Intracerebroventricular injection of an
anti-GDNF antibody impaired the learning and memory of control rats. Since neuroinflammation is an
early neuropathological process for surgery-induced cognitive dysfunction in adults, neurogenesis and
dendritic arborization are important for learning and memory, and GDNF inhibits neuroinflammation
and enhances neurogenesis and dendritic arborization, we hypothesize that surgery reduces GDNF,
which then heightens neuroinflammation and decreases neurogenesis and dendritic arborization, to
induce learning and memory impairment and that reduction of GDNF in the urine is a biomarker for
anesthesia and surgery-induced learning and memory impairment. In this project, we will determine
whether: 1) anesthesia and surgery reduce growth factors including GDNF in young rats; 2) decrease
of GDNF in the urine predicts learning and memory impairment after surgery; and 3) GDNF decrease
leads to heightened neuroinflammation and impairment of neurogenesis and dendritic development in
the brain. P7 rats will be subjected to right carotid arterial exploration or laparotomy under sevoflurane
anesthesia. Learning and memory will be evaluated by Barnes maze and fear conditioning. Brains will
be harvested for biochemical examination and determination of brain cell genesis and dendritic
arborization. Urine GDNF levels will be quantified. Receiver operating characteristic (ROC) curves will
be constructed to assess the value of using urine GDNF levels as a biomarker for surgery-induced
learning and memory impairment. These studies will identify possible biomarkers for surgery-induced
learning and memory impairment in the neonatal rats. They will also reveal the effects of GDNF on
neuroinflammation and the long-term brain structural changes in developing brain after surgery.

## Key facts

- **NIH application ID:** 10246802
- **Project number:** 5R01HD089999-05
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** ZHIYI ZUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,410
- **Award type:** 5
- **Project period:** 2017-09-11 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246802

## Citation

> US National Institutes of Health, RePORTER application 10246802, Glial cell line-derived neurotropic factor and postoperative cognitive impairment in young rats (5R01HD089999-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10246802. Licensed CC0.

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