# Role of Netrin-1 in staging hypoxic ischemic encephalopathy

**Authors:** Nur Aycan, Derya Çay Demir, Eyyüp Yürektürk, Murat Başaranoglu, Serap Karaman, Oğuz Tuncer

PMC · DOI: 10.1590/1806-9282.20241889 · 2025-06-16

## TL;DR

This study explores how Netrin-1 levels in the blood can help stage and predict outcomes for babies with hypoxic-ischemic encephalopathy.

## Contribution

The study identifies Netrin-1 as a potential biomarker for staging hypoxic-ischemic encephalopathy and assessing therapeutic hypothermia outcomes.

## Key findings

- Serum Netrin-1 levels were significantly higher in moderate and severe HIE patients undergoing therapeutic hypothermia.
- Netrin-1 levels did not significantly differ in mild HIE patients compared to controls.
- Netrin-1 correlated with lactate, uric acid, and lactate dehydrogenase levels in HIE patients.

## Abstract

The diagnosis and prognosis of neonatal hypoxic-ischemic encephalopathy are established through clinical evidence and laboratory, imaging, and electrophysiological assessments of the nervous system. Netrin-1 was the first axon guidance molecule identified as a critical component of embryonic development in vertebrates and has a solid chemotropic function for angiogenesis, morphogenesis, cell migration, and axonal guidance. It was hypothesized that Netrin-1 will differ at different hypoxic-ischemic encephalopathy stages.

This study included 75 hospitalized hypoxic-ischemic encephalopathy newborns and 48 healthy newborns born at the same hospital and followed up only by their mothers. Demographic, laboratory, and Netrin-1 data were evaluated for all hypoxic-ischemic encephalopathy stages.

Serum Netrin-1 concentrations were significantly greater in patients with moderate and severe hypoxic-ischemic encephalopathy who underwent therapeutic hypothermia than in controls and patients with severe hypoxic-ischemic encephalopathy. However, serum Netrin-1 concentrations were not significantly greater in patients with mild hypoxic-ischemic encephalopathy than in controls. In 75 hypoxic-ischemic encephalopathy patients, correlations of Netrin-1 with lactate, uric acid, and lactate dehydrogenase were statistically significant (p=0.0001, 0.008, and 0.043, respectively).

Netrin-1 significantly increased in moderate and severe patients. Therefore, this marker could be a biomarker for staging hypoxic-ischemic encephalopathy and therapeutic hypothermia and predicting the prognosis of neonatal hypoxic-ischemic encephalopathy patients.

## Linked entities

- **Proteins:** Ntn1 (netrin 1)
- **Chemicals:** lactate (PubChem CID 61503), uric acid (PubChem CID 1175)
- **Diseases:** hypoxic-ischemic encephalopathy (MONDO:0006663)

## Full-text entities

- **Genes:** NTN1 (netrin 1) [NCBI Gene 9423] {aka MRMV4, NET1, NTN1L}
- **Diseases:** hypothermia (MESH:D007035), hypoxic ischemic encephalopathy (MESH:D020925)
- **Chemicals:** lactate (MESH:D019344), uric acid (MESH:D014527)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12172530