{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:40:50Z","timestamp":1777927250414,"version":"3.51.4"},"reference-count":74,"publisher":"SAGE Publications","issue":"17","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p>\n                    Females have been understudied in pre-clinical and clinical traumatic brain injury (TBI), despite distinct biology and worse clinical outcomes versus males. Sulfonylurea receptor 1 (SUR1) inhibition has shown promising results in predominantly male TBI. A phase II trial is ongoing. We investigated whether SUR1 inhibition effects on contusional TBI differ by sex given that this may inform clinical trial design and\/or interpretation. We studied the moderating effects of sex on post-injury brain tissue loss in 142 male and female ATP-binding cassette transporter subfamily C member 8 (\n                    <jats:italic toggle=\"yes\">Abcc8<\/jats:italic>\n                    ) wild-type, heterozygote, and knockout mice (12\u201315 weeks). Monkey fibroblast-like cells and mouse brain endothelium-derived cells were used for\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    studies. Mice were injured with controlled cortical impact and euthanized 21 days post-injury to assess contusion, brain, and hemisphere volumes (vs. genotype- and sex-matched na\u00efves).\n                    <jats:italic toggle=\"yes\">Abcc8<\/jats:italic>\n                    knockout mice had smaller contusion volumes (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.012) and larger normalized contralateral (right) hemisphere volumes (nRHV;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.03) after injury versus wild type. This was moderated by sex: Contusions were smaller (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.020), nRHV was higher (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.001), and there was less global atrophy (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.003) in male, but not female, knockout versus wild-type mice after TBI. Less atrophy occurred in males for each copy of\n                    <jats:italic toggle=\"yes\">Abcc8<\/jats:italic>\n                    lost (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.023\u20130.002, all outcomes).\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    , sex-determining region Y (SRY) stimulated\n                    <jats:italic toggle=\"yes\">Abcc8<\/jats:italic>\n                    promoter activity and increased\n                    <jats:italic toggle=\"yes\">Abcc8<\/jats:italic>\n                    expression. Loss of\n                    <jats:italic toggle=\"yes\">Abcc8<\/jats:italic>\n                    strongly protected against post-traumatic cerebral atrophy in male, but not female, mice. This may partly be mediated by SRY on the Y-chromosome. Sex differences may have important implications for ongoing and future trials of SUR1 blockade.\n                  <\/jats:p>","DOI":"10.1089\/neu.2021.0105","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T01:13:02Z","timestamp":1620090782000},"page":"2473-2485","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["<i>Abcc8<\/i>\n                    (Sulfonylurea Receptor-1) Impact on Brain Atrophy after Traumatic Brain Injury Varies by Sex"],"prefix":"10.1177","volume":"38","author":[{"given":"Swathi","family":"Tata","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin E.","family":"Zusman","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick M.","family":"Kochanek","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volodymyr","family":"Gerzanich","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Seong","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Kyoon","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S.B.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keri","family":"Janesko-Feldman","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent A.","family":"Vagni","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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