ATF3 is a neuron‐specific biomarker for spinal cord injury and ischaemic stroke
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Le résumé fourni par la source
BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- ATF3 is a neuron‐specific biomarker for spinal cord injury and ischaemic stroke
- Date Crossref
- 01/04/2024
- Éditeur
- Wiley
- 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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University of California Department of Anesthesia and Perioperative Care pays non établi dans la noticeUniversité ou école supérieure
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People's Hospital of Cangzhou pays non établi dans la noticeÉtablissement de santé
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Shandong University Department of Anesthesiology Shandong Provincial Hospital pays non établi dans la noticeUniversité ou école supérieure
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Shandong Provincial Hospital pays non établi dans la noticeÉtablissement de santé
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Shandong Provincial QianFoShan Hospital pays non établi dans la noticeÉtablissement de santé
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Nanchang University Department of Anesthesiology The Second Affiliated Hospital pays non établi dans la noticeUniversité ou école supérieure
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Second Affiliated Hospital of Nanchang University pays non établi dans la noticeÉtablissement de santé
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Guangzhou Medical University Department of Anesthesiology pays non établi dans la noticeUniversité ou école supérieure
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Capital Medical University Department of Pain Management Xuanwu Hospital pays non établi dans la noticeUniversité ou école supérieure
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University of California San Francisco Medical Center pays non établi dans la noticeÉtablissement de santé
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Tianjin Medical University General Hospital Department of Neurosurgery pays non établi dans la noticeÉtablissement de santé
Department of Anesthesia and Perioperative Care — University of California, People's Hospital of Cangzhou et Department of Anesthesiology Shandong Provincial Hospital — Shandong University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.