{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:10:46Z","timestamp":1790143846385,"version":"4.0.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is predominantly expressed in microglia within the central nervous system (CNS) and plays critical roles in neuroinflammatory diseases, including traumatic brain injury (TBI). The function of the microglial NLRP3 inflammasome may vary as the disease progresses. A comprehensive understanding of these dynamic alterations is essential for opti-mizing the therapeutic time window. Post-TBI, microglial NLRP3 levels exhib-ited significant elevation, and microglial-specific NLRP3 conditional knockout (NLRP3-CKO) reduced neurological and neuropathological impairments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptome sequencing was performed at baseline and on days 1, 3, and 7 post-TBI using injured cortical tissue from NLRP3-CKO mice and their litter-mate controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Notable transcriptional changes occurred on day 3 post-TBI, while fewer differentially expressed genes (DEGs) were identified at other time points. NLRP3-CKO influenced macrophage polarization on day 1 and neuronal cell survival on day 3 post-injury. In addition, NLRP3-CKO significantly reduced the upregulation of pyroptosis-related genes and the dysregulation of genes associ-ated with neuroinflammation and neuropathology after TBI. Gene set enrichment analysis (GSEA) indicated diverse potential regulatory pathways at various time points. The temporal profiles of gene expression were also analyzed, revealing distinct expression trends in several gene clusters, particularly on day 7 post-TBI. Pathway enrichment analysis of overlapping genes in these clusters identified several relevant pathways, which were further validated through quantitative real-time polymerase chain reaction (qPCR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Overall, these findings elucidate the dynamic effects of microglial NLRP3 on transcriptomic alterations during the acute phase of TBI and highlight potential regulatory pathways, offering insights into NLRP3 inflammasome-related pathological mechanisms and enhancing the optimization of therapeutic time windows for TBI.<\/jats:p>\n                  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Center, State Key Laboratory of Trauma and Chemical Poisoning, Department of Army Occupational Disease, Da-ping Hospital, Army Medical University (Third Military Medical University)","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"The Molecular Biology Center, State Key Laboratory of Trauma and Chemical Poisoning, Department of Army Occupational Disease, Da-ping Hospital, Army Medical University (Third Military Medical University)","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Luo","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell and Tissue 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