{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:24:48Z","timestamp":1788791088231,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>For post-menopausal women, stroke is complicated by the variable effects of estrogen therapy and the age-related therapeutic consequences involved. Estrogen therapy has been shown to have an age-dimorphic effect, which is neuroprotective in young females, but non-neuroprotective, even neurotoxic in acyclic females. We hypothesized that arterial baroreflex (ABR) and its downstream acetylcholine-\u03b17 nicotinic acetylcholine receptor (\u03b17nAChR) anti-inflammatory pathways are involved in estrogen efficacy toward cerebral ischemic damage. Our data showed that estrogen supplements contributed to ABR improvement and neuroprotection in adult, not aged, ovariectomized (OVX) rats. In adult rats, OVX-induced estrogen deficiency aggravated middle cerebral artery occlusion (MCAO), which induced brain infarction and reduced ABR function, with decreased \u03b17nAChR expression of the brain and exaggerated inflammation following MCAO; these effects were significantly prevented by supplementation with estrogen. ABR impairment by sinoaortic denervation partly attenuated the estrogen effect on baroreflex sensitivity (BRS) and ischemic damage in adult rats, as well as \u03b17nAChR expression and inflammatory response. These data suggested that ABR and acetylcholine-\u03b17nAChR anti-inflammatory pathways are involved in the neuroprotection of estrogen in adult OVX rats. In contrast, aged rats exhibited more severe ischemic damage and inflammatory response than adult rats, as well as poorer baroreflex function and lower \u03b17nAChR expression. Estrogen supplements did not improve BRS or confer neuroprotection in aged rats without affecting brain \u03b17nAChR and post-ischemic inflammation. Most importantly, ketanserin restored ABR function and significantly postponed the onset of stroke in aged female strokeprone spontaneously hypertensive rats, whereas estrogen treatment failed to delay the development of stroke. Our findings reveal that estrogen is protective against ischemic stroke (IS) in adult female rats and that ABR played a role in this beneficial action. Dysfunction of ABR and unresponsiveness to estrogen in aged female rats may contribute to a reduced estrogen efficacy against cerebral ischemia.<\/jats:p>","DOI":"10.3389\/fnagi.2023.1167170","type":"journal-article","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T10:11:56Z","timestamp":1683022316000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia"],"prefix":"10.3389","volume":"15","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Min","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1007\/s11906-006-0080-1","article-title":"Estrogen and hypertension","volume":"8","author":"Ashraf","year":"2006","journal-title":"Curr. 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