{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:49:24Z","timestamp":1791589764046,"version":"4.3.4"},"reference-count":27,"publisher":"Georg Thieme Verlag KG","issue":"04","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Department of Science and Technology, New Delhi, India","award":["SR\/WOS-A\/LS-656\/2016"],"award-info":[{"award-number":["SR\/WOS-A\/LS-656\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Asian J Neurosurg"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The prevalence of intracranial aneurysms (IAs) and aneurysmal subarachnoid hemorrhage (aSAH) due to IA rupture, is higher in postmenopausal compared with premenopausal women and men in the same age group. This is presumably due to reduced levels of the vascular protective hormone, estradiol. Experimental studies have revealed direct effects of estradiol on the vascular endothelium. Our aim was to determine the influence of estradiol and estrogen receptors on cerebral vasculature and the role of estrogen-mediated nitric oxide (NO) pathway in the formation and rupture of IAs.<\/jats:p>\n                  <jats:p>We measured circulatory estradiol and NO levels and the relative expression of genes involved in estrogen-mediated NO synthesis in 349 aSAH patients and 360 age- and gender-matched controls. We observed significantly reduced serum estradiol and NO levels in aSAH patients compared with controls.<\/jats:p>\n                  <jats:p>The expression of endothelial NO synthase gene (NOS3), estrogen receptor genes (ESR1, ESR2), and the kinases (SRC, AKT1, PIK3R1) involved in NO synthesis was significantly reduced in IA tissues compared with controls. Serum estradiol positively and significantly correlated with NO levels.<\/jats:p>\n                  <jats:p>Our results indicate that the activity of endothelial NO synthase and the bioavailability of NO may be regulated by estradiol and estrogen receptors to maintain cerebral vascular tone.<\/jats:p>","DOI":"10.1055\/s-0046-1819694","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T23:00:16Z","timestamp":1775862016000},"page":"740-746","source":"Crossref","is-referenced-by-count":0,"title":["Influence of Estradiol and Estrogen Receptors on NOS3 Expression and Nitric Oxide Release: Implications for Intracranial Aneurysm Formation and Rupture"],"prefix":"10.1055","volume":"21","author":[{"given":"Shruthi Shimoga","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0024-4748","authenticated-orcid":false,"given":"Rita","family":"Christopher","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India"},{"name":"Integrative Medical Research Department, PES University Institute of Medical Sciences and Research, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagavatula Indira","family":"Devi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhananjaya Ishwar","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhaval","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.wneu.2018.04.143","article-title":"Hemodynamic stress, inflammation, and intracranial aneurysm development and rupture: a systematic review","volume":"115","author":"F Signorelli","year":"2018","journal-title":"World Neurosurg"},{"issue":"07","key":"ref2","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S1474-4422(11)70109-0","article-title":"Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis","volume":"10","author":"M H Vlak","year":"2011","journal-title":"Lancet Neurol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"720141","DOI":"10.1155\/2015\/720141","article-title":"Relationship between postmenopausal estrogen deficiency and aneurysmal subarachnoid hemorrhage","volume":"2015","author":"S Tabuchi","year":"2015","journal-title":"Behav Neurol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1161\/01.HYP.25.4.848","article-title":"Circulating nitric oxide (nitrite\/nitrate) levels in postmenopausal women substituted with 17 \u03b2-estradiol and norethisterone acetate. 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