{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:58:52Z","timestamp":1780498732025,"version":"3.54.1"},"reference-count":37,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>Apoptosis is implicated in vasospasm and long-term sequelae of subarachnoid hemorrhage (SAH). The authors observed that 17\u03b2-estradiol (E2) can attenuate cerebral vasospasm, lower endothelin-1 production, and preserve normal endothelial nitric oxide synthase expression by reduction of inducible NO synthase expression in experimental SAH. The authors investigated the potential antiapoptotic effects of E2 in an experimental rat model of SAH.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>The authors examined the antiapoptotic effects of E2 in a double-hemorrhage SAH model in male Sprague-Dawley rats. The rats underwent subcutaneous implantation of a Silastic tube containing corn oil either with or without E2, and some E2-treated animals also received ICI 182,780 (a nonselective estrogen receptor [ER] antagonist) for 7 days after SAH. The degree of vasospasm was determined by averaging the cross-sectional areas of the basilar artery 7 days after SAH. The expression of apoptotic indicators, including TNF-\u03b1, caspase 3, Bcl-2, Bax, terminal deoxynucleotidyl transferase\u2013mediated deoxyuridine triphosphate nick end labeling (TUNEL), and cell death assays were used for detection of apoptosis.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Treatment with E2 significantly attenuated SAH-induced vasospasm. Seven days after the induction of SAH, positive TUNEL-staining was seen, and DNA fragmentation was increased in the dentate gyrus. Increased TNF-\u03b1 and cleaved caspase-3 protein expression and decreased Bcl-2 protein expression in the dentate gyrus were also observed. These changes were reversed with E2-treatment but not in the presence of ICI 182,780. However, the expression of Bax did not change after SAH either with or without E2 treatment.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The authors found that E2 appears to confer an antiapoptotic effect that reduces secondary brain injury after SAH via estrogen receptor\u2013dependent mechanisms. This finding provides support for possible future applications of E2 treatment for the reduction of secondary injury after SAH in patients.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2009.3.jns081660","type":"journal-article","created":{"date-parts":[[2009,5,8]],"date-time":"2009-05-08T16:13:15Z","timestamp":1241799195000},"page":"1014-1022","source":"Crossref","is-referenced-by-count":15,"title":["Attenuation of subarachnoid hemorrhage\u2013induced apoptotic cell death with 17 beta-estradiol"],"prefix":"10.3171","volume":"111","author":[{"given":"Chih-Lung","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurosurgery,"},{"name":"Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron S.","family":"Dumont","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Feng","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zen-Kong","family":"Dai","sequence":"additional","affiliation":[{"name":"Faculty of Medicine,"},{"name":"Division of Cardiology and Pulmonology, Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juei-Tang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee-Jean","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jih-Hui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of 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