{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:39:51Z","timestamp":1793054391258,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000104","name":"National Aeronautics and Space Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The amino acid homocysteine (HCY) has been implicated in the pathobiology of several conditions, including spaceflight\u2010associated neuro\u2010ocular syndrome (SANS)\u2014a collection of symptoms affecting near vision in astronauts. Blood\u2010retinal barrier (BRB) and blood\u2013brain barrier (BBB) dysfunctions are implicated in the pathobiology of SANS. Our objective was to assess how HCY affects BRB\/BBB permeability and the role of the NLRP3 inflammasome in the modulation of such effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human brain and retinal microvascular endothelial cells (HBMECs and HRMECs) were treated with 100\u2009\u03bcM HCY alone or in conjunction with NLRP3 inflammasome inhibitor MCC950 at 1\u2009\u03bcM. The assays performed included fluorometric assays to measure cell viability, an enzyme assay for caspase\u20101, expression of BRB\/BBB tight junction protein zonula occludens\u20101 (ZO\u20101) by RT\u2010PCR, and barrier permeability using FITC\u2010dextran.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In HRMECs and HBMECs, HCY\u2010induced endothelial monolayer hyperpermeability significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). In HBMECs, the effect was attenuated by MCC950 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Increased Caspase\u20101 activity was observed in both cell types following the addition of HCY. Following HCY addition, gene expression results denoting barrier damage were observed, particularly that of ZO\u20101 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HCY induces hyperpermeability in retinal and brain endothelial cells. NLRP3\u2010mediation in HCY\u2010induced microvascular permeability is prominent in brain endothelial cells compared to retinal endothelial cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/micc.70019","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T16:13:28Z","timestamp":1752768808000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Homocysteine Induces Brain and Retinal Microvascular Endothelial Cell Barrier Damage and Hyperpermeability via\n                    <scp>NLRP3<\/scp>\n                    Inflammasome Pathway Differentially"],"prefix":"10.1111","volume":"32","author":[{"given":"O'lisa Yaa","family":"Waithe","sequence":"first","affiliation":[{"name":"Department of Surgery and Neuroscience Institute Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9115-5379","authenticated-orcid":false,"given":"Aliyah","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Surgery and Neuroscience Institute Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saravanakumar","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"Department of Surgery and Neuroscience Institute Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela M.","family":"Seplovich","sequence":"additional","affiliation":[{"name":"Department of Surgery and Neuroscience Institute Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binu","family":"Tharakan","sequence":"additional","affiliation":[{"name":"Department of Surgery and Neuroscience Institute Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-018-0070-y"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000778"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.111.154245"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030393"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10517-006-0202-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2013.877933"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021071"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126259"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8010121"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.577325"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14977"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNO.0000000000000852"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308501"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105165"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10081119"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09731-y"},{"key":"e_1_2_9_18_1","first-page":"2883","article-title":"Correlation Between the Levels of NLRP3, Hcy, IL\u20101\u03b2, IL\u201018 and the Prognosis in Patients With Hemorrhagic Stroke","volume":"13","author":"Li Q.","year":"2021","journal-title":"American Journal of Translational 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