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International Journal of Legal Medicine

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20.06.2023 | Original Article

Proteomic analysis discovers potential biomarkers of early traumatic axonal injury in the brainstem

verfasst von: Qianling Chen, Lingyue Li, Luyao Xu, Bin Yang, Yuebing Huang, Dongfang Qiao, Xia Yue

Erschienen in: International Journal of Legal Medicine | Ausgabe 1/2024

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Abstract

Objective

Application of Tandem Mass Tags (TMT)-based LC–MS/MS analysis to screen for differentially expressed proteins (DEPs) in traumatic axonal injury (TAI) of the brainstem and to predict potential biomarkers and key molecular mechanisms of brainstem TAI.

Methods

A modified impact acceleration injury model was used to establish a brainstem TAI model in Sprague–Dawley rats, and the model was evaluated in terms of both functional changes (vital sign measurements) andstructural changes (HE staining, silver-plating staining and β-APP immunohistochemical staining). TMT combined with LC–MS/MS was used to analyse the DEPs in brainstem tissues from TAI and Sham groups. The biological functions of DEPs and potential molecular mechanisms in the hyperacute phase of TAI were analysed by bioinformatics techniques, and candidate biomarkers were validated using western blotting and immunohistochemistry on brainstem tissues from animal models and humans.

Results

Based on the successful establishment of the brainstem TAI model in rats, TMT-based proteomics identified 65 DEPs, and bioinformatics analysis indicated that the hyperacute phase of TAI involves multiple stages of biological processes including inflammation, oxidative stress, energy metabolism, neuronal excitotoxicity and apoptosis. Three DEPs, CBR1, EPHX2 and CYP2U1, were selected as candidate biomarkers and all three proteins were found to be significantly expressed in brainstem tissue 30 min-7 days after TAI in both animal models and humans.

Conclusion

Using TMT combined with LC–MS/MS analysis for proteomic study of early TAI in rat brainstem, we report for the first time that CBR1, EPHX2 and CYP2U1 can be used as biomarkers of early TAI in brainstem by means of western blotting and immunohistochemical staining, compensating for the limitations of silver-plating staining and β-APP immunohistochemical staining, especially in the case of very short survival time after TAI (shorter than 30 min). A number of other proteins that also have a potential marker role are also presented, providing new insights into the molecular mechanisms, therapeutic targets and forensic identification of early TAI in brainstem.

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Titel: Proteomic analysis discovers potential biomarkers of early traumatic axonal injury in the brainstem
verfasst von: Qianling Chen
Lingyue Li
Luyao Xu
Bin Yang
Yuebing Huang
Dongfang Qiao
Xia Yue
Publikationsdatum: 20.06.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: International Journal of Legal Medicine / Ausgabe 1/2024
Print ISSN: 0937-9827
Elektronische ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-023-03039-5

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Proteomic analysis discovers potential biomarkers of early traumatic axonal injury in the brainstem

Abstract

Objective

Methods

Results

Conclusion

Neu im Fachgebiet Rechtsmedizin

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Objective

Methods

Results

Conclusion

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