ArticleBMC neuroscience2025
Esketamine attenuates traumatic brain injury by modulating STAT3-mediated Glycolysis and immune responses.
Article in BMC neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cortical Neuroprotective Mechanisms of Exercise Training in Post-Traumatic Brain Injury: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- The Effect of Esketamine Combined with Pulsed Radiofrequency on Neuropathic Pain in Herpes Zoster Patients: A Randomised Clinical Trial.Pain and therapy · 2026Article
- Protein Lactylation in Central Nervous System Diseases: Molecular Mechanisms and Targeted Therapeutic Strategies.International journal of nanomedicine · 2026Review
- Esketamine Attenuates Postoperative Neurocognitive Disorder in Aged Mice: Associations with Bioenergetic Remodeling in Hippocampal CD11b-Enriched Cell Fractions and Glycolysis-Related Signaling.Drug design, development and therapy · 2026Article
- T Cell Involvement in Neuroinflammation After Traumatic Brain Injury: Implications for Therapeutic Intervention.CNS neuroscience & therapeutics · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
backgroundSecondary injury following traumatic brain injury (TBI) involves neuroinflammation, immune cell infiltration, and metabolic dysregulation, leading to progressive neurological damage. This study evaluates the potential of esketamine, an NMDA receptor antagonist, to modulate immune responses, inhibit glycolysis, and mitigate secondary brain injury in a TBI mouse model.
methodsMale C57BL/6J mice were subjected to controlled cortical impact to induce TBI. Mice were treated with esketamine, either alone or combined with the STAT3 activator colivelin, or the glycolysis inhibitor 2-deoxyglucose (2-DG). Neurological function, BBB permeability, immune cell infiltration, macrophage polarization, and glycolytic activity were assessed using immunohistochemistry, flow cytometry, quantitative PCR, and enzyme-linked immunosorbent assay (ELISA).
resultsEsketamine treatment significantly reduced structural brain tissue damage, including contusions, tissue loss, and edema, while also improving neurological outcomes in TBI mice. Mechanistically, esketamine inhibited CD4 + T cell activation and suppressed Th17 differentiation both in vivo and in vitro. It also promoted a shift in macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Further analysis revealed that esketamine blocked STAT3 activation, which in turn reduced the expression of glycolytic genes (e.g., Hk2, Pgk1, Aldoa) essential for Th17 cell proliferation and M1 polarization. Co-treatment with colivelin reversed esketamine's effects on STAT3-mediated glycolysis, while 2-DG enhanced its anti-inflammatory actions.
conclusionEsketamine attenuates TBI-induced neuroinflammation and tissue damage by inhibiting STAT3-mediated glycolysis, thus reducing Th17 and M1 macrophage activity and promoting regulatory and reparative immune responses. These findings highlight esketamine's potential as a therapeutic option for TBI, targeting both immune modulation and metabolic pathways to alleviate secondary injury. CLINICAL TRIAL NUMBER: not applicable.
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