{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:34:20Z","timestamp":1781109260016,"version":"3.54.1"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,9,25]]},"abstract":"<jats:p>\n                    The relationship between stressful life events and the onset of\n disease is well documented. However, the role of psychological stress\n as a risk factor for life-threatening cerebrovascular insults such as\n stroke remains unspecified, but could explain individual variation in\n stroke outcome. To discover the mechanisms through which psychological\n stress may alter stroke outcome, we modeled the effects of chronic\n social intimidation and stress on ischemia-induced\n                    <jats:italic>bcl-2<\/jats:italic>\n                    expression and early neuronal cell loss resulting from cerebral artery\n occlusion in mice (C57BL\/6). The\n                    <jats:italic>bcl-2<\/jats:italic>\n                    protooncogene\n promotes cell survival and protects against apoptosis and\n cellular necrosis in numerous neurodegenerative disorders, including\n stroke. In our study, male mice were chronically exposed to aggressive\n social stimuli before induction of a controlled, mild ischemic insult.\n Stressed mice expressed \u224870% less\n                    <jats:italic>bcl-2<\/jats:italic>\n                    mRNA than\n unstressed mice after ischemia. In addition, social stress greatly\n exacerbated infarct in wild-type mice but not in transgenic mice that\n constitutively express increased neuronal\n                    <jats:italic>bcl-2<\/jats:italic>\n                    . Despite\n similar postischemic concentrations of corticosterone, the major stress\n hormone in mice, high corticosterone concentrations were significantly\n correlated with larger infarcts in wild-type mice but not\n                    <jats:italic>bcl-2<\/jats:italic>\n                    transgenic mice. Thus, enhanced\n                    <jats:italic>bcl-2<\/jats:italic>\n                    expression offsets the potentially deleterious\n consequences of high postischemic plasma corticosterone concentrations.\n Taken together, these data demonstrate that stressful prestroke social\n milieu strongly compromises an endogenous molecular\n mechanism of neuroprotection in injured brain and offer a new\n behavioral target for stroke therapy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.201215298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"11824-11828","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":126,"title":["Social stress exacerbates stroke outcome by suppressing\n                    <i>Bcl-2<\/i>\n                    expression"],"prefix":"10.1073","volume":"98","author":[{"given":"A. Courtney","family":"DeVries","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns\r Hopkins University School of Medicine, Baltimore, MD 21287; and\r Molecular Neurobiology Laboratory, The Walter and Eliza\r Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Dong","family":"Joh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns\r Hopkins University School of Medicine, Baltimore, MD 21287; and\r Molecular Neurobiology Laboratory, The Walter and Eliza\r Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ora","family":"Bernard","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns\r Hopkins University School of Medicine, Baltimore, MD 21287; and\r Molecular Neurobiology Laboratory, The Walter and Eliza\r Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimihiko","family":"Hattori","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns\r Hopkins University School of Medicine, Baltimore, MD 21287; and\r Molecular Neurobiology Laboratory, The Walter and Eliza\r Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia D.","family":"Hurn","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns\r Hopkins University School of Medicine, Baltimore, MD 21287; and\r Molecular Neurobiology Laboratory, The Walter and Eliza\r Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Traystman","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns\r Hopkins University School of Medicine, Baltimore, MD 21287; and\r Molecular Neurobiology Laboratory, The Walter and Eliza\r Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil J.","family":"Alkayed","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns\r Hopkins University School of Medicine, Baltimore, MD 21287; and\r Molecular Neurobiology Laboratory, The Walter and Eliza\r Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,9,11]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.psych.50.1.137"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.53.12.1024"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.21.2.223"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/00207458108985837"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.11.2329"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.27.11.1999"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000411300"},{"key":"e_1_3_3_8_2","first-page":"1113","volume":"8","author":"Gentry W D","year":"1979","unstructured":"W D Gentry, C D Jenkins, B H Kaplan, A Heyman, M S Breslin, D T Gianturco Heart Lung 8, 1113\u20131116 (1979).","journal-title":"Heart Lung"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.20.7.850"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1977.03280140052016"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(93)90083-B"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1990.tb00213.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1986.72"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.4035356"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199607000-00008"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.05-05-01228.1985"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(98)80008-1"},{"key":"e_1_3_3_18_2","unstructured":"Alkayed N. 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