{"corpus_id":246739728,"paper_sha":"69c0e31871d32fa8b06f5bb41017c4638ec77890","doi":"10.1016/j.jss.2022.01.021","arxiv_id":null,"pmid":35151055,"pmcid":null,"mag_id":null,"dblp_id":null,"acl_id":null,"title":"Minocycline Pretreatment Prevents Blood-Brain Barrier Disruption in Septic Rats.","year":2022,"publication_date":"2022-02-09","venue":"Journal of Surgical Research","journal":{"name":"The Journal of surgical research","pages":"\n          247-254\n        ","volume":"273"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine"],"reference_count":27,"citation_count":12,"influential_citation_count":1,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Blood-Brain Barrier","mj":true,"ui":"D001812"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Matrix Metalloproteinase 9","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D020780"},{"d":"Minocycline","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pharmacology","mj":false,"ui":"Q000494"},{"q":"therapeutic use","mj":false,"ui":"Q000627"}],"ui":"D008911"},{"d":"Occludin","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D062793"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Rats, Sprague-Dawley","mj":false,"ui":"D017207"},{"d":"Saline Solution","mj":false,"ui":"D000077330"},{"d":"Sepsis","mj":true,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D018805"}],"chemicals":[{"n":"Occludin","ui":"D062793","reg":"0"},{"n":"Saline Solution","ui":"D000077330","reg":"0"},{"n":"Matrix Metalloproteinase 9","ui":"D020780","reg":"EC 3.4.24.35"},{"n":"Minocycline","ui":"D008911","reg":"FYY3R43WGO"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"INTRODUCTION\nThe aim of the study was to explore the mechanism by which minocycline protects the blood-brain barrier (BBB) in septic rats.\n\n\nMETHODS\nA sepsis rat model was generated in healthy, male Sprague-Dawley rats by cecal ligation and puncture (CLP). The rats were randomly divided into four groups and treated as follows: sham-operated plus normal saline (Sham + S group), CLP plus normal saline (CLP + S group), CLP plus minocycline pretreatment (CLP + M1 group), and CLP plus minocycline treatment (CLP + M2 group). Rats in the CLP + M1 group received 45 mg/kg minocycline by intraperitoneal injection every 12 h for 72 h. Rats in the Sham + S and CLP + S groups were injected with the same volume of normal saline every 12 h for 72 h. Rats in the CLP + M2 group were intraperitoneally injected with 45 mg/kg minocycline immediately after CLP and once every 12 h for 72 h. All rats were sacrificed at 72 h after operation. Tumor necrosis factor α and interleukin 6 levels, the expression of ionized calcium-binding adaptor molecule-1 (Iba-1), and the permeability of the BBB were measured. The expression of matrix metalloproteinases-9 (MMP-9) and the tight junction proteins zonula occludens-1 (ZO-1) and occludin was detected by Western blot. In addition, Evans blue (EB) staining, immunohistochemistry, and ELISA analysis were carried out.\n\n\nRESULTS\nMinocycline pretreatment significantly inhibited microglial activation, decreased the sepsis-induced expression of MMP-9, increased the expression of ZO-1 and occludin, and improved the permeability of the BBB. Minocycline treatment failed to inhibit microglial activation, decrease the sepsis-induced expression of MMP-9, increase the expression of ZO-1 or occluding, or improve the permeability of the BBB.\n\n\nCONCLUSIONS\nMinocycline pretreatment can effectively improve the altered permeability of the BBB caused by sepsis. The mechanism may be related to the inhibition of microglial activation and MMP-9 expression and increased expression of ZO-1 and occludin.","claims":[{"public_id":"cl_dfec6a4dfa9cb839946ef60d40a691ab","status":"active","text":"Minocycline pretreatment inhibits microglial activation, decreases sepsis-induced matrix metalloproteinase-9 expression, increases zonula occludens-1 and occludin expression, and improves blood-brain barrier permeability in septic rats.","confidence":0.9,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_dfec6a4dfa9cb839946ef60d40a691ab"},{"public_id":"cl_bf340d5637fca6086d08da88cade47e0","status":"active","text":"Minocycline treatment started immediately after cecal ligation and puncture fails to inhibit microglial activation, decrease matrix metalloproteinase-9 expression, increase zonula occludens-1 or occludin expression, or improve blood-brain barrier permeability.","confidence":0.85,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_bf340d5637fca6086d08da88cade47e0"}],"concepts":[{"public_id":"co_09aec70d1d00061af2471fcca1434811","status":"active","name":"cecal ligation and puncture","description":"A surgical procedure used to induce polymicrobial sepsis in the rat model used in this study.","types":["method"],"aliases":["CLP"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_09aec70d1d00061af2471fcca1434811"},{"public_id":"co_0d210b2f3c9ff3abcf44b8258d7f85dc","status":"active","name":"sepsis","description":"A systemic inflammatory condition induced in rats by cecal ligation and puncture to model septic brain injury.","types":["condition"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0d210b2f3c9ff3abcf44b8258d7f85dc"},{"public_id":"co_1d205bd4af5259f2e2ca050d247addb9","status":"active","name":"zonula occludens-1","description":"A tight junction scaffolding protein at the blood-brain barrier whose expression was measured by Western blot in this study.","types":["protein"],"aliases":["ZO-1"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_1d205bd4af5259f2e2ca050d247addb9"},{"public_id":"co_54e4e428b53d0adb34a9dfdf0299985f","status":"active","name":"minocycline pretreatment","description":"An intervention in which minocycline (45 mg/kg intraperitoneally, every 12 h for 72 h) was administered to rats prior to cecal ligation and puncture-induced sepsis.","types":["intervention","experimental group"],"aliases":["CLP + M1 group"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_54e4e428b53d0adb34a9dfdf0299985f"},{"public_id":"co_6a3425a7c65be5ca476ca9aef138c569","status":"active","name":"ionized calcium-binding adaptor molecule-1","description":"A marker protein used to detect and quantify microglial activation in brain tissue in this study.","types":["protein marker"],"aliases":["Iba-1"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_6a3425a7c65be5ca476ca9aef138c569"},{"public_id":"co_6c1cf32bafc0886e896a72f760dd2751","status":"active","name":"minocycline treatment","description":"An intervention in which minocycline (45 mg/kg intraperitoneally, every 12 h for 72 h) was administered to rats starting immediately after cecal ligation and puncture.","types":["intervention","experimental group"],"aliases":["CLP + M2 group"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_6c1cf32bafc0886e896a72f760dd2751"},{"public_id":"co_8de8d15726bd7f450af75de44d38414f","status":"active","name":"microglial activation","description":"The activation state of microglia in brain tissue, assessed via ionized calcium-binding adaptor molecule-1 expression as an indicator of neuroinflammation.","types":["biological process"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_8de8d15726bd7f450af75de44d38414f"},{"public_id":"co_9bf390b8ab645a4d602c897fd7102109","status":"active","name":"blood-brain barrier permeability","description":"A measure of how readily substances cross the blood-brain barrier, assessed here by Evans blue staining as an indicator of barrier integrity.","types":["outcome","measurement"],"aliases":["BBB permeability"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_9bf390b8ab645a4d602c897fd7102109"},{"public_id":"co_9c1849a80840240437c81035a75190c4","status":"active","name":"occludin","description":"A transmembrane tight junction protein at the blood-brain barrier whose expression was measured by Western blot in this study.","types":["protein"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_9c1849a80840240437c81035a75190c4"},{"public_id":"co_a08f0f2457f5e71c778db4d7efc36fe6","status":"active","name":"blood-brain barrier","description":"The selective barrier separating brain tissue from circulating blood, whose disruption in sepsis was studied here.","types":["anatomical structure"],"aliases":["BBB"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a08f0f2457f5e71c778db4d7efc36fe6"},{"public_id":"co_da3e5377fe6844a0015bdfccf13888fc","status":"active","name":"matrix metalloproteinase-9","description":"An enzyme capable of degrading tight junction proteins, measured by Western blot as an indicator of blood-brain barrier breakdown.","types":["protein","enzyme"],"aliases":["MMP-9"],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_da3e5377fe6844a0015bdfccf13888fc"}],"external_ids":{"DOI":"10.1016/j.jss.2022.01.021","ArXiv":null,"PubMed":35151055,"PubMedCentral":null,"MAG":null,"DBLP":null,"ACL":null},"open_access":{"is_open_access":false,"pdf_url":null,"landing_url":"https://sah.borca.ai/papers/246739728","source":null,"pdf_url_source":null,"license":null,"reason":"pdf_url_not_indexed"},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":631468,"paper_uid":"37b1597a-4fff-448e-850c-5c5118d9bfe7","canonical_identity":{"paper_id":631468,"paper_uid":"37b1597a-4fff-448e-850c-5c5118d9bfe7","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/246739728"}