# Hypobaric hypoxia aggravates neuroinflammation in ligature-induced periodontitis mice via the STAT3 signaling pathway

**Authors:** Lu Chen, Jiayi Zhang, Xuechao Fei, Jiajing Wang, Jiayue Gao, Xiangpei Yue, Yaqun Jiang, Zibi Shi, Shaojie Zhang, Xiufang Jiang, Wenyue Chang, Zhonghua Dai, Jianjun Guo, Tong Zhao, Xiaoxia Jiang, Lingling Zhu

PMC · DOI: 10.3389/fimmu.2025.1600035 · Frontiers in Immunology · 2025-07-29

## TL;DR

This study shows that hypobaric hypoxia worsens neuroinflammation in mice with periodontitis, likely through the STAT3 signaling pathway.

## Contribution

The study reveals a novel mechanism linking hypobaric hypoxia and periodontitis through STAT3 pathway activation.

## Key findings

- Hypobaric hypoxia significantly worsens periodontal and neuroinflammation in mice with periodontitis.
- Hippocampal microglia are activated after brief hypobaric hypoxia exposure in these mice.
- The STAT3 signaling pathway is crucial in mediating the heightened neuroinflammation observed.

## Abstract

Studies have shown that inflammation is a key risk factor for altitude sickness in hypobaric hypoxia environments. Periodontitis, a common oral disease, is prevalent among many individuals. This study aimed to investigate the onset and progression of neuroinflammation in mice with ligature-induced periodontitis under hypobaric hypoxia and to explore the potential underlying mechanisms.

C57BL/6J mice were randomly divided into four groups: control (Con), hypobaric hypoxia (HH), periodontitis (P), and periodontitis combined with hypobaric hypoxia (PHH), which were then placed in a hypobaric hypoxia chamber for 1, 3, and 5 days. The expression of inflammatory cytokines was assessed by qPCR or ELISA. Anxiety-related behavior and memory abilities were evaluated by behavioral tests. The activation of microglia and astrocytes in the hippocampus and cortex was assessed by immunofluorescence.

Our results demonstrated that one day of exposure to hypobaric hypoxia in mice with periodontitis significantly exacerbated periodontal inflammation, peripheral inflammation, and neuroinflammation. Specifically, hippocampal microglia in these mice were activated following brief exposure to hypobaric hypoxia. Furthermore, the STAT3 signaling pathway was markedly activated, playing a crucial role in mediating the intensified neuroinflammation observed in periodontitis model mice subjected to one day of hypobaric hypoxia.

Our data highlight the exacerbating effect of hypobaric hypoxia on neuroinflammation in periodontitis model mice, mediated through the activation of the STAT3 signaling pathway. These findings provide important insights and considerations for individuals with periodontitis who are planning to travel to high-altitude regions.

## Linked entities

- **Proteins:** STAT3 (signal transducer and activator of transcription 3)
- **Diseases:** periodontitis (MONDO:0005076)

## Full-text entities

- **Genes:** Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}
- **Diseases:** altitude sickness (MESH:D000532), hypoxia (MESH:D000860), Periodontitis (MESH:D010518), neuroinflammation (MESH:D000090862), Anxiety (MESH:D001007), oral disease (MESH:D009059), inflammation (MESH:D007249)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12339329/full.md

## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12339329/full.md

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Source: https://tomesphere.com/paper/PMC12339329