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Microglial pyroptosis, a form of programmed cell death associated with inflammation, has been implicated in exacerbating neuroinflammation and secondary injury following TBI. Compound porcine cerebroside ganglioside injection (CPCGI) has shown anti\u2010inflammatory and antioxidant properties, but its effects on pyroptosis remain unexplored. This study investigates the role of CPCGI in TBI and its underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A controlled cortical impact (CCI) model was utilized to establish TBI in\u00a0vivo, while lipopolysaccharide (LPS) was used in\u00a0vitro to induce microglial activation that mimicked TBI conditions. The effects of CPCGI on microglial pyroptosis and inflammatory cytokines were analyzed through immunofluorescence, flow cytometry, western blotting, and quantitative real\u2010time PCR (qRT\u2010PCR). The involvement of the NLRP3 inflammasome in CPCGI's mechanism was examined using NLRP3 overexpression or the NLRP3 agonist BMS\u2010986299. A microglia\u2013neuron interaction model was created, and neuronal injury was assessed with the Cell Counting Kit\u20108 and Fluoro\u2010Jade C (FJC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with CPCGI resulted in significant improvement in the neurobehavioral outcomes, reduced lesion volume, and decreased neuronal loss following TBI. Notably, TBI induced microglial pyroptosis and the release of pro\u2010inflammatory cytokines, while CPCGI inhibited microglial pyroptosis, thereby mitigating the inflammatory response and reducing neuronal damage. Mechanistically, overexpression of NLRP3 in microglial cells reversed the inhibitory effects of CPCGI on microglial pyroptosis, indicating that CPCGI's inhibition of microglial pyroptosis may be mediated by the NLRP3 inflammasome. Furthermore, NLRP3 overexpression or administration of the NLRP3 agonist BMS\u2010986299 negated the neuroprotective effects of CPCGI in\u00a0vivo and in\u00a0vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that CPCGI provides neuroprotection in TBI by targeting NLRP3 inflammasome\u2010mediated microglial pyroptosis, thereby improving the neuroinflammatory microenvironment and promoting neurological recovery. This underscores its potential as a promising candidate for TBI treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70322","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T05:57:17Z","timestamp":1741759037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>CPCGI<\/scp>\n                    Alleviates Neural Damage by Modulating Microglial Pyroptosis After Traumatic Brain Injury"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0933-4499","authenticated-orcid":false,"given":"Lu\u2010Lu","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Neurology Beijing Tiantan Hospital, Capital Medical University  Beijing China"},{"name":"China National Clinical Research Center for Neurological Diseases  Beijing 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