Cargando…

Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Lei, Wang, Jia, Shan, Qing, Shu, He, Guo, Jin-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186347/
https://www.ncbi.nlm.nih.gov/pubmed/37205058
http://dx.doi.org/10.3389/fnagi.2023.1167170
_version_ 1785042540360105984
author Wang, Lei
Wang, Jia
Shan, Qing
Shu, He
Guo, Jin-Min
author_facet Wang, Lei
Wang, Jia
Shan, Qing
Shu, He
Guo, Jin-Min
author_sort Wang, Lei
collection PubMed
description 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-α7 nicotinic acetylcholine receptor (α7nAChR) 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 α7nAChR 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 α7nAChR expression and inflammatory response. These data suggested that ABR and acetylcholine-α7nAChR 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 α7nAChR expression. Estrogen supplements did not improve BRS or confer neuroprotection in aged rats without affecting brain α7nAChR 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.
format Online
Article
Text
id pubmed-10186347
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-101863472023-05-17 Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia Wang, Lei Wang, Jia Shan, Qing Shu, He Guo, Jin-Min Front Aging Neurosci Aging Neuroscience 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-α7 nicotinic acetylcholine receptor (α7nAChR) 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 α7nAChR 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 α7nAChR expression and inflammatory response. These data suggested that ABR and acetylcholine-α7nAChR 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 α7nAChR expression. Estrogen supplements did not improve BRS or confer neuroprotection in aged rats without affecting brain α7nAChR 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. Frontiers Media S.A. 2023-05-02 /pmc/articles/PMC10186347/ /pubmed/37205058 http://dx.doi.org/10.3389/fnagi.2023.1167170 Text en Copyright © 2023 Wang, Wang, Shan, Shu and Guo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging Neuroscience
Wang, Lei
Wang, Jia
Shan, Qing
Shu, He
Guo, Jin-Min
Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia
title Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia
title_full Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia
title_fullStr Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia
title_full_unstemmed Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia
title_short Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia
title_sort involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186347/
https://www.ncbi.nlm.nih.gov/pubmed/37205058
http://dx.doi.org/10.3389/fnagi.2023.1167170
work_keys_str_mv AT wanglei involvementofbaroreflexdeficiencyintheagerelatedlossofestrogenefficacyagainstcerebralischemia
AT wangjia involvementofbaroreflexdeficiencyintheagerelatedlossofestrogenefficacyagainstcerebralischemia
AT shanqing involvementofbaroreflexdeficiencyintheagerelatedlossofestrogenefficacyagainstcerebralischemia
AT shuhe involvementofbaroreflexdeficiencyintheagerelatedlossofestrogenefficacyagainstcerebralischemia
AT guojinmin involvementofbaroreflexdeficiencyintheagerelatedlossofestrogenefficacyagainstcerebralischemia