{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:05:05Z","timestamp":1790831105628,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic cerebral hypoperfusion (CCH) is a neurological disorder characterized by persistent insufficiency of cerebral blood flow, yet specific biomarkers and mechanistic insights are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study integrated transcriptomic and proteomic multi-omics analyses, along with behavioral assessments and immunofluorescence validation in a bilateral common carotid artery stenosis (BCAS) mouse model, to identify and validate candidate multi-omics biomarkers of CCH and explore their potential druggability. Leveraging public transcriptomic datasets and in-house proteomic data, differential expression analysis, protein-protein interaction network construction, and five topological algorithms identified\n                      <jats:italic>Tlr2<\/jats:italic>\n                      ,\n                      <jats:italic>Anxa5<\/jats:italic>\n                      , and\n                      <jats:italic>Grin2a<\/jats:italic>\n                      as candidate biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BCAS mice exhibited spatial memory impairments in behavioral tests. Immunofluorescence revealed upregulated\n                      <jats:italic>TLR2<\/jats:italic>\n                      and\n                      <jats:italic>ANXA5<\/jats:italic>\n                      , downregulated\n                      <jats:italic>GRIN2A,<\/jats:italic>\n                      and increased TLR2-IBA1 co-localization indicating microglial activation.\n                      <jats:italic>Tlr2<\/jats:italic>\n                      and\n                      <jats:italic>Anxa5<\/jats:italic>\n                      positively correlated with infiltrating immune cells, whereas Grin2a showed a negative correlation. A putative ceRNA network and in silico molecular docking suggested strong binding of pirinixic acid to both TLR2 and ANXA5.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Tlr2<\/jats:italic>\n                      ,\n                      <jats:italic>Anxa5<\/jats:italic>\n                      , and\n                      <jats:italic>Grin2a<\/jats:italic>\n                      can serve as candidate multi-omics signature molecules of CCH in the mouse brain, with consistent alterations at the transcriptomic, proteomic, and tissue levels.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1911864","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:51:08Z","timestamp":1790830268000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross-dataset transcriptomics\u2013proteomics analysis identifies Tlr2, Anxa5, and Grin2a as candidate mouse-brain signatures associated with chronic cerebral hypoperfusion"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiang","family":"Fan","sequence":"first","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]},{"name":"Department of Neurology, Sichuan Provincial People's Hospital","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Yu","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sichuan Provincial People's Hospital","place":["Chengdu, China"]},{"name":"School of Clinical Medicine, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sichuan Provincial People's Hospital","place":["Chengdu, China"]},{"name":"School of Clinical Medicine, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]},{"name":"Department of Neurology, Sichuan Provincial People's Hospital","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]},{"name":"Department of Neurology, Sichuan Provincial People's Hospital","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sichuan Provincial People's Hospital","place":["Chengdu, China"]},{"name":"School of Clinical Medicine, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sichuan Provincial People's Hospital","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Hu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]},{"name":"Department of Neurology, Sichuan Provincial People's 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