# Mild hypothermia effects on serum neuroprotection, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and superoxide dismutase (SOD) levels in neonates with hypoxic-ischemic encephalopathy

**Authors:** Wenfeng Duan, Xuan Wang

PMC · DOI: 10.5937/jomb0-50866 · Journal of Medical Biochemistry · 2025-06-13

## TL;DR

Mild hypothermia improves brain health markers and recovery in newborns with hypoxic-ischemic encephalopathy.

## Contribution

This study identifies potential biomarkers for evaluating treatment response in neonatal HIE using mild hypothermia.

## Key findings

- Mild hypothermia improved neural cytokines (NGF, BDNF) and brain injury markers (S100B, NSE, MBP) in HIE neonates.
- Oxidative stress factors (SOD, MDA, IL-18, caspase-3) were significantly reduced in the hypothermia group.
- Neonates treated with mild hypothermia showed faster neurological recovery and higher response rates compared to controls.

## Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is a serious condition that can lead to long-term neurological damage. Mild hypothermia is a promising treatment for HIE, but its efficacy and safety in newborns are not well established. To evaluate the therapeutic effects of mild hypothermia on neonatal HIE in a randomised controlled trial.

This was a prospective study of 132 newborns with HIE treated with either mild hypothermia or routine conventional treatment. The primary outcome measures were changes in neural cytokines, brain injury markers, oxidative stress factors, neurological function recovery time, and therapeutic outcomes.

The mild hypothermia group showed significant improvements in neural cytokines (NGF and BDNF), brain injury markers (S100B, NSE, and MBP), and oxidative stress factors (SOD, MDA, IL-18, and caspase-3) compared to the control group. The mild hypothermia group also had a faster neurological function recovery time and a higher total response rate (95.45% vs. 80.30%, P<0.05) compared to the control group.

Mild hypothermia therapy is a safe and effective treatment for neonatal HIE, with significant improvements in neural cytokines, brain injury markers, and oxidative stress factors, as well as faster neurological function recovery time and higher therapeutic outcomes. Results: The mild hypothermia group showed significant improvements in neural cytokines (NGF and BDNF), brain injury markers (S100B, NSE, and MBP), and oxidative stress factors (SOD, MDA, IL-18, and caspase-3) compared to the control group. The mild hypothermia group also had a faster neurological function recovery time and a higher total response rate (95.45% vs. 80.30%, P<0.05) compared to the control group. Conclusions: Mild hypothermia therapy is a safe and effective treatment for neonatal HIE, with significant improvements in neural cytokines, brain injury markers, and oxidative stress factors, as well as faster neurological function recovery time and higher therapeutic outcomes. The novelty of this work was that it showed potential biomarkers for evaluating response to treatment and the pathophysiological effect of treatment by assessing these biomarkers.

## Linked entities

- **Proteins:** NGF (nerve growth factor), BDNF (brain derived neurotrophic factor), S100B (S100 calcium binding protein B), ENO2 (enolase 2), MBP (myelin basic protein), SOD1 (superoxide dismutase 1), so (sine oculis), IL18 (interleukin 18), Casp3 (caspase 3)
- **Diseases:** hypoxic-ischemic encephalopathy (MONDO:0006663), HIE (MONDO:0006663)

## Full-text entities

- **Genes:** NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, MBP (myelin basic protein) [NCBI Gene 4155], IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}
- **Diseases:** HIE (MESH:D020925), neurological damage (MESH:D020196), brain injury (MESH:D001930), hypothermia (MESH:D007035)
- **Chemicals:** MDA (MESH:D015104)

## Full text

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## Figures

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## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12357617/full.md

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Source: https://tomesphere.com/paper/PMC12357617