High-altitude hypoxia aggravated neurological deficits in mice induced by traumatic brain injury via BACH1 mediating astrocytic ferroptosis
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Le résumé fourni par la source
Traumatic brain injury (TBI) is one of the leading causes of disability and mortality, which was classified as low-altitude TBI and high-altitude TBI. A large amount of literature shows that high-altitude TBI is associated with more severe neurological impairments and higher mortality rates compared to low-altitude TBI, due to the special environment of high-altitude hypoxia. However, the role of high-altitude hypoxia in the pathogenesis of TBI remains unclear. In order to deeply investigate this scientific issue, we constructed a high-altitude hypoxic TBI model at different altitudes and used animal behavioral assessments (Modified neurological severity score, rotarod test, elevated plus maze test) as well as histopathological analyses (brain gross specimens, brain water content, Evans blue content, hypoxia inducible factor-1α, Hematoxylin-Eosin staining and ROS detection) to reveal its underlying principles and characteristics. We found that with higher altitude, TBI-induced neurological deficits were more severe and the associated histopathological changes were more significant. Single-nuclear RNA sequencing was subsequently employed to further reveal differential gene expression profiles in high-altitude TBI. We found a significant increase in ferroptosis of astrocytes in cases of high-altitude TBI compared to those at low-altitude TBI. Analyzing transcription factors in depth, we found that Bach1 plays a crucial role in regulating key molecules that induce ferroptosis in astrocytes following high-altitude TBI. Down-regulation of Bach1 can effectively alleviate high-altitude TBI-induced neurological deficits and histopathological changes in mice. In conclusion, high-altitude hypoxia may significantly enhance the ferroptosis of astrocytes and aggravate TBI by up-regulating Bach1 expression. Our study provides a theoretical foundation for further understanding of the mechanism of high-altitude hypoxic TBI and targeted intervention therapy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- High-altitude hypoxia aggravated neurological deficits in mice induced by traumatic brain injury via BACH1 mediating astrocytic ferroptosis
- Date Crossref
- 05/02/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Xijing Hospital pays non établi dans la noticeÉtablissement de santé
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Air Force Medical University pays non établi dans la noticeUniversité ou école supérieure
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Northwest University pays non établi dans la noticeUniversité ou école supérieure
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Fuzhou Dermatosis Prevention Hospital pays non établi dans la noticeÉtablissement de santé
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Fuzhou Pulmonary Hospital of Fujian pays non établi dans la noticeÉtablissement de santé
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Fourth Military Medical University Department of Neurosurgery pays non établi dans la noticeUniversité ou école supérieure
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College of Life Sciences pays non établi dans la noticeUniversité ou école supérieure
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Fuzhou 900th Hospital Department of Neurosurgery pays non établi dans la noticeÉtablissement de santé
Xijing Hospital, Air Force Medical University et Northwest University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.