{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:53Z","timestamp":1792788833170,"version":"4.5.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Xiangnan University","id":[{"id":"https:\/\/ror.org\/05by9mg64","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis-associated encephalopathy (SAE) is a neurological complication of sepsis characterized by cognitive impairment and persistent brain dysfunction. Although neuroinflammation and glial activation contribute to SAE pathogenesis, the molecular alterations underlying hippocampal neuroimmune dysfunction remain incompletely understood. The potential role of NaHCO\u2083 in SAE-associated neurological dysfunction remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An LPS-induced mouse model of SAE was established to investigate the effects of NaHCO\u2083 administration. Survival and cognitive function were evaluated using survival analysis, novel object recognition, open-field, and Y-maze tests. Hippocampal transcriptomic and proteomic profiling was performed, followed by cross-omics integration. Candidate molecules were further assessed by qRT-PCR, Western blotting, and immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NaHCO\u2083 treatment improved survival and alleviated cognitive deficits in SAE mice. Transcriptomic and proteomic profiling revealed extensive hippocampal molecular alterations, with functional enrichment highlighting immune- and inflammation-related processes and pathways. Three-group cross-omics analysis identified 18 candidates meeting an FDR\u202f&amp;lt;\u202f0.05 at both omics levels and showing a concordant SAE-associated increase followed by a decrease after NaHCO\u2083 treatment. Among these candidates, C3 was prioritized based on its cross-omics expression pattern and neuroimmune relevance. qRT-PCR and Western blot analyses supported increased hippocampal C3 expression during SAE and its responsiveness to NaHCO\u2083 treatment. Immunofluorescence analysis revealed increased spatial association between C3 and GFAP-positive astrocytic structures during SAE, which was attenuated following NaHCO\u2083 treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NaHCO\u2083 treatment was associated with improved neurological outcomes and altered hippocampal molecular profiles in LPS-induced SAE. Cross-omics analysis identified C3 among candidate molecules associated with SAE and NaHCO\u2083 responsiveness. The increased C3\u2013GFAP spatial association suggests that complement-associated alterations accompany astrocytic responses during SAE. The causal role of C3 and the mechanisms underlying the effects of NaHCO\u2083 require further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1954272","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:20:26Z","timestamp":1791372026000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated transcriptomic and proteomic profiling reveals C3-associated hippocampal neuroimmune remodeling in sodium bicarbonate-treated sepsis-associated encephalopathy"],"prefix":"10.3389","volume":"20","author":[{"given":"Housheng","family":"Deng","sequence":"first","affiliation":[{"name":"The First People's Hospital of Chenzhou, Medical Education Center of Jinan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Ling","sequence":"additional","affiliation":[{"name":"The First People's Hospital of Chenzhou, Medical Education Center of Jinan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lie","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Suzhou Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuli","family":"He","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First People's Hospital of Chenzhou, Medical Education Center of Jinan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"106525","DOI":"10.1016\/j.phrs.2022.106525","article-title":"Can a basic solution activate the inflammatory reflex? 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