• The medulla oblongata undergoes secondary injury after striking the cortex. • Neurotoxic astrocytes are activated in the ventral medulla oblongata after injury. • Proteomic analysis discovers potential biomarkers after injury. The medulla oblongata undergoes secondary injury after striking the cortex. Neurotoxic astrocytes are activated in the ventral medulla oblongata after injury. Proteomic analysis discovers potential biomarkers after injury. Unclear mechanisms of secondary injury in the medulla oblongata (MO) after traumatic brain injury (TBI) prompted the exploration of the relationship between astrocyte phenotype changes in the MO and neuroinflammation after TBI, providing new insights into the pathogenesis of TBI. In this study, C57BL/6J mice were randomly divided into sham and closed-TBI groups. Pathophysiological changes after TBI were evaluated via physiological parameter monitoring and cardiac ultrasound. We identified differentially expressed proteins (DEPs) and analyzed the secondary mechanisms of injury through proteomics. Hematoxylin and eosin (HE) staining was used to observe morphological changes in the cortex and ventral region of the MO after TBI. The protein expression levels of IL-1β, TNF-α, GFAP, C3 (A1), and S100A10 (A2) were detected via Western blotting. Astrocyte distribution and polarization were evaluated via immunofluorescence. Proteomic analysis revealed multiple secondary changes in the MO after TBI. Among the 48 common DEPs, UCP2, FBXW5, and ADIPOR2 were revealed to regulate inflammation. TBI reduced the respiratory rate, ejection fraction, and shortening fraction. HE staining revealed edema, neuronal eosinophilia, and astrocyte activation with red cytoplasmic staining in the ventral MO. Western blotting and immunofluorescence confirmed increased IL-1β and TNF-α expression and neurotoxic reactive astrocyte activation in the ventral MO. Together, neurotoxic reactive astrocyte activation-mediated neuroinflammation underlies acute MO injury after TBI. FBXW5 and ADIPOR2 expression changes over time postinjury. These findings provide a molecular basis for the time course of TBI in forensics along with new insights into the mechanism underlying the acute inflammatory phase and post-TBI injury progression.
Chen et al. (Sun,) studied this question.