The effects of different doses of estradiol (E2) on cerebral ischemia in an in vitro model of oxygen and glucose deprivation and reperfusion and in a rat model of middle carotid artery occlusion
Because neuroprotective effects of estrogen remain controversial, we aimed to investigate the effect of different doses of estradiol (E2) on cerebral ischemia using both in vivo and in vitro experiments. PC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 μM and 20 μM)...
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| Veröffentlicht in: | BMC neuroscience 2013-10, Vol.14 (1), p.118-118, Article 118 |
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| creator | Ma, Yu-Long Qin, Pei Li, Yan Shen, Lan Wang, Shi-Quan Dong, Hai-Long Hou, Wu-Gang Xiong, Li-Ze |
| description | Because neuroprotective effects of estrogen remain controversial, we aimed to investigate the effect of different doses of estradiol (E2) on cerebral ischemia using both in vivo and in vitro experiments.
PC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 μM and 20 μM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu) incorporation and flow cytometric analysis showed that physiological doses of E2 enhanced cell proliferation and pharmacological doses of E2 inhibited cell proliferation. After the cells were exposed to oxygen and glucose deprivation (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, flow cytometric analysis and Western blot analysis showed that physiological doses of E2 enhanced cell viability, reduced cell apoptosis and decreased the expression of pro-apoptotic protein caspase-3. In contrast, pharmacological doses of E2 decreased cell viability and induced cell apoptosis. In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was induced for 2 h using the middle cerebral artery occlusion (MCAO) technique, followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that 6 μg/kg and 20 μg/kg E2 replacement induced an increase in neurological deficit scores, a decrease in the infarct volume and a reduction in the expression of caspase-3 when compared to animals in the OVX group without E2 treatment. However, 50 μg/kg E2 replacement treatment decreased neurological deficit scores, increased the infarct volume and the expression of caspase-3 when compared to animals in the control group and 6 up/kg or 20 μg/kg E2 replacement group.
We conclude that physiological levels of E2 exhibit neuroprotective effects on cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2 have damaging effects on neurons after cerebral ischemia. |
| doi_str_mv | 10.1186/1471-2202-14-118 |
| format | Article |
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PC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 μM and 20 μM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu) incorporation and flow cytometric analysis showed that physiological doses of E2 enhanced cell proliferation and pharmacological doses of E2 inhibited cell proliferation. After the cells were exposed to oxygen and glucose deprivation (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, flow cytometric analysis and Western blot analysis showed that physiological doses of E2 enhanced cell viability, reduced cell apoptosis and decreased the expression of pro-apoptotic protein caspase-3. In contrast, pharmacological doses of E2 decreased cell viability and induced cell apoptosis. In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was induced for 2 h using the middle cerebral artery occlusion (MCAO) technique, followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that 6 μg/kg and 20 μg/kg E2 replacement induced an increase in neurological deficit scores, a decrease in the infarct volume and a reduction in the expression of caspase-3 when compared to animals in the OVX group without E2 treatment. However, 50 μg/kg E2 replacement treatment decreased neurological deficit scores, increased the infarct volume and the expression of caspase-3 when compared to animals in the control group and 6 up/kg or 20 μg/kg E2 replacement group.
We conclude that physiological levels of E2 exhibit neuroprotective effects on cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2 have damaging effects on neurons after cerebral ischemia.</description><identifier>ISSN: 1471-2202</identifier><identifier>EISSN: 1471-2202</identifier><identifier>DOI: 10.1186/1471-2202-14-118</identifier><identifier>PMID: 24106772</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Blotting, Western ; Brain - drug effects ; Brain - metabolism ; Brain - pathology ; Brain damage ; Brain Ischemia - metabolism ; Brain Ischemia - pathology ; Caspase 3 - analysis ; Caspase 3 - biosynthesis ; Cell proliferation ; Cell Survival - drug effects ; Cerebral ischemia ; Disease Models, Animal ; Dosage and administration ; Dose-Response Relationship, Drug ; Drug therapy ; Estradiol ; Estradiol - administration & dosage ; Estrogens ; Female ; Flow Cytometry ; Hormone replacement therapy ; Infarction, Middle Cerebral Artery - metabolism ; Infarction, Middle Cerebral Artery - pathology ; Medical research ; Neurons - drug effects ; Neurons - metabolism ; Neuroprotective Agents - administration & dosage ; PC12 Cells ; Rats ; Rats, Sprague-Dawley ; Recovery of Function - drug effects ; Reperfusion Injury - metabolism ; Reperfusion Injury - pathology ; Rodents ; Womens health</subject><ispartof>BMC neuroscience, 2013-10, Vol.14 (1), p.118-118, Article 118</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Ma et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2013 Ma et al.; licensee BioMed Central Ltd. 2013 Ma et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b617t-ae8bbf992f6d5ad8ceef7fe08d856fb92bbed8ca0645fd18b69e2dd4b1f53e243</citedby><cites>FETCH-LOGICAL-b617t-ae8bbf992f6d5ad8ceef7fe08d856fb92bbed8ca0645fd18b69e2dd4b1f53e243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851874/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851874/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24106772$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Yu-Long</creatorcontrib><creatorcontrib>Qin, Pei</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Shen, Lan</creatorcontrib><creatorcontrib>Wang, Shi-Quan</creatorcontrib><creatorcontrib>Dong, Hai-Long</creatorcontrib><creatorcontrib>Hou, Wu-Gang</creatorcontrib><creatorcontrib>Xiong, Li-Ze</creatorcontrib><title>The effects of different doses of estradiol (E2) on cerebral ischemia in an in vitro model of oxygen and glucose deprivation and reperfusion and in a rat model of middle carotid artery occlusion</title><title>BMC neuroscience</title><addtitle>BMC Neurosci</addtitle><description>Because neuroprotective effects of estrogen remain controversial, we aimed to investigate the effect of different doses of estradiol (E2) on cerebral ischemia using both in vivo and in vitro experiments.
PC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 μM and 20 μM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu) incorporation and flow cytometric analysis showed that physiological doses of E2 enhanced cell proliferation and pharmacological doses of E2 inhibited cell proliferation. After the cells were exposed to oxygen and glucose deprivation (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, flow cytometric analysis and Western blot analysis showed that physiological doses of E2 enhanced cell viability, reduced cell apoptosis and decreased the expression of pro-apoptotic protein caspase-3. In contrast, pharmacological doses of E2 decreased cell viability and induced cell apoptosis. In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was induced for 2 h using the middle cerebral artery occlusion (MCAO) technique, followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that 6 μg/kg and 20 μg/kg E2 replacement induced an increase in neurological deficit scores, a decrease in the infarct volume and a reduction in the expression of caspase-3 when compared to animals in the OVX group without E2 treatment. However, 50 μg/kg E2 replacement treatment decreased neurological deficit scores, increased the infarct volume and the expression of caspase-3 when compared to animals in the control group and 6 up/kg or 20 μg/kg E2 replacement group.
We conclude that physiological levels of E2 exhibit neuroprotective effects on cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2 have damaging effects on neurons after cerebral ischemia.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Brain damage</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Caspase 3 - analysis</subject><subject>Caspase 3 - biosynthesis</subject><subject>Cell proliferation</subject><subject>Cell Survival - drug effects</subject><subject>Cerebral ischemia</subject><subject>Disease Models, Animal</subject><subject>Dosage and administration</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug therapy</subject><subject>Estradiol</subject><subject>Estradiol - administration & dosage</subject><subject>Estrogens</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Hormone replacement therapy</subject><subject>Infarction, Middle Cerebral Artery - metabolism</subject><subject>Infarction, Middle Cerebral Artery - pathology</subject><subject>Medical research</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neuroprotective Agents - administration & dosage</subject><subject>PC12 Cells</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Recovery of Function - drug effects</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - pathology</subject><subject>Rodents</subject><subject>Womens health</subject><issn>1471-2202</issn><issn>1471-2202</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1Uk1r3DAQNaUlSdPceyqCXtqDE0u2bPlSCEv6AYFc0rPQx2hXwba2kr1k_15_WcfZZJOFFIM9evPeYzTPWfaRFueUivqCVg3NGStYTqsckTfZyR56-6I-zt6ndFcUtBEVO8qOWUWLumnYSfb3dgUEnAMzJhIcsR7rCMNIbEjwAEEao7I-dOTLFftKwkAMMnRUHfHJrKD3iviBqGF-b_wYA-mDhW7WhvvtEuaeJctuMmhJLKyj36jRhx0eYQ3RTenpPFuRqMZnk95b2wExKobRW6LiCHFLgjHdg-pD9s6pLsHZ4_c0-_396nbxM7---fFrcXmd65o2Y65AaO3alrnacmWFAXCNg0JYwWunW6Y1IKqKuuLOUqHrFpi1laaOl8Cq8jT7tvNdT7oHa3BJuAOJt-lV3MqgvDzsDH4ll2EjS8GpaGaDxc5A-_Afg8OOCb2cM5RzhlhJjBhdPj-OEcOfCcORd2GKA94cGRXlDS95-8xaqg6kH1xAR9NjYPKSlxWvBWMlss5fYeFjMVUTBnAe8QNBsROYGFKK4PbT02Kern5t3k8v17YXPP2D5T93-uBg</recordid><startdate>20131009</startdate><enddate>20131009</enddate><creator>Ma, Yu-Long</creator><creator>Qin, Pei</creator><creator>Li, Yan</creator><creator>Shen, Lan</creator><creator>Wang, Shi-Quan</creator><creator>Dong, Hai-Long</creator><creator>Hou, Wu-Gang</creator><creator>Xiong, Li-Ze</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20131009</creationdate><title>The effects of different doses of estradiol (E2) on cerebral ischemia in an in vitro model of oxygen and glucose deprivation and reperfusion and in a rat model of middle carotid artery occlusion</title><author>Ma, Yu-Long ; Qin, Pei ; Li, Yan ; Shen, Lan ; Wang, Shi-Quan ; Dong, Hai-Long ; Hou, Wu-Gang ; Xiong, Li-Ze</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b617t-ae8bbf992f6d5ad8ceef7fe08d856fb92bbed8ca0645fd18b69e2dd4b1f53e243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Brain damage</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - pathology</topic><topic>Caspase 3 - analysis</topic><topic>Caspase 3 - biosynthesis</topic><topic>Cell proliferation</topic><topic>Cell Survival - drug effects</topic><topic>Cerebral ischemia</topic><topic>Disease Models, Animal</topic><topic>Dosage and administration</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug therapy</topic><topic>Estradiol</topic><topic>Estradiol - administration & dosage</topic><topic>Estrogens</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Hormone replacement therapy</topic><topic>Infarction, Middle Cerebral Artery - metabolism</topic><topic>Infarction, Middle Cerebral Artery - pathology</topic><topic>Medical research</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neuroprotective Agents - administration & dosage</topic><topic>PC12 Cells</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Recovery of Function - drug effects</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - pathology</topic><topic>Rodents</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Yu-Long</creatorcontrib><creatorcontrib>Qin, Pei</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Shen, Lan</creatorcontrib><creatorcontrib>Wang, Shi-Quan</creatorcontrib><creatorcontrib>Dong, Hai-Long</creatorcontrib><creatorcontrib>Hou, Wu-Gang</creatorcontrib><creatorcontrib>Xiong, Li-Ze</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Yu-Long</au><au>Qin, Pei</au><au>Li, Yan</au><au>Shen, Lan</au><au>Wang, Shi-Quan</au><au>Dong, Hai-Long</au><au>Hou, Wu-Gang</au><au>Xiong, Li-Ze</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effects of different doses of estradiol (E2) on cerebral ischemia in an in vitro model of oxygen and glucose deprivation and reperfusion and in a rat model of middle carotid artery occlusion</atitle><jtitle>BMC neuroscience</jtitle><addtitle>BMC Neurosci</addtitle><date>2013-10-09</date><risdate>2013</risdate><volume>14</volume><issue>1</issue><spage>118</spage><epage>118</epage><pages>118-118</pages><artnum>118</artnum><issn>1471-2202</issn><eissn>1471-2202</eissn><abstract>Because neuroprotective effects of estrogen remain controversial, we aimed to investigate the effect of different doses of estradiol (E2) on cerebral ischemia using both in vivo and in vitro experiments.
PC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 μM and 20 μM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu) incorporation and flow cytometric analysis showed that physiological doses of E2 enhanced cell proliferation and pharmacological doses of E2 inhibited cell proliferation. After the cells were exposed to oxygen and glucose deprivation (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, flow cytometric analysis and Western blot analysis showed that physiological doses of E2 enhanced cell viability, reduced cell apoptosis and decreased the expression of pro-apoptotic protein caspase-3. In contrast, pharmacological doses of E2 decreased cell viability and induced cell apoptosis. In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was induced for 2 h using the middle cerebral artery occlusion (MCAO) technique, followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that 6 μg/kg and 20 μg/kg E2 replacement induced an increase in neurological deficit scores, a decrease in the infarct volume and a reduction in the expression of caspase-3 when compared to animals in the OVX group without E2 treatment. However, 50 μg/kg E2 replacement treatment decreased neurological deficit scores, increased the infarct volume and the expression of caspase-3 when compared to animals in the control group and 6 up/kg or 20 μg/kg E2 replacement group.
We conclude that physiological levels of E2 exhibit neuroprotective effects on cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2 have damaging effects on neurons after cerebral ischemia.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24106772</pmid><doi>10.1186/1471-2202-14-118</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Blotting, Western Brain - drug effects Brain - metabolism Brain - pathology Brain damage Brain Ischemia - metabolism Brain Ischemia - pathology Caspase 3 - analysis Caspase 3 - biosynthesis Cell proliferation Cell Survival - drug effects Cerebral ischemia Disease Models, Animal Dosage and administration Dose-Response Relationship, Drug Drug therapy Estradiol Estradiol - administration & dosage Estrogens Female Flow Cytometry Hormone replacement therapy Infarction, Middle Cerebral Artery - metabolism Infarction, Middle Cerebral Artery - pathology Medical research Neurons - drug effects Neurons - metabolism Neuroprotective Agents - administration & dosage PC12 Cells Rats Rats, Sprague-Dawley Recovery of Function - drug effects Reperfusion Injury - metabolism Reperfusion Injury - pathology Rodents Womens health |
| title | The effects of different doses of estradiol (E2) on cerebral ischemia in an in vitro model of oxygen and glucose deprivation and reperfusion and in a rat model of middle carotid artery occlusion |
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