{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:28:51Z","timestamp":1793305731081,"version":"4.5.0"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873262"],"award-info":[{"award-number":["81873262"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81804038"],"award-info":[{"award-number":["81804038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>\n                      Cerebral ischemia\u2010reperfusion (I\/R) injury is a major factor underlying the high mortality and morbidity rates in stroke patients. Our previous study found that the combination of\n                      <jats:italic>Astragalus membranaceus<\/jats:italic>\n                      extract and ligustrazine (Ast+Lig) treatment could protect brain tissues against inflammation in rats with thrombolytic cerebral ischemia. Activation of N\u2010methyl\u2010D\u2010aspartate receptors (NMDAR) is implicated in brain damage induced by cerebral I\/R injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used in vivo and in vitro models of cerebral I\/R injury for middle cerebral artery occlusion\/reperfusion in mice and oxygen\u2010glucose deprivation\/reoxygenation in primary rat cerebral cortical neurons to evaluate the protective effects of Ast+Lig on cerebral I\/R injury, and whether the protective mechanism was related to the regulation of NMDAR\u2010ERK\/CREB signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Treatment with Ast+Lig, or MK\u2010801 (an inhibitor of NMDAR) significantly ameliorated neurological deficits, decreased infarct volumes, suppressed neuronal damage and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx, and maintained the mitochondrial membrane potential in vivo and in vitro following cerebral I\/R injury based on 2,3,5\u2010triphenyl tetrazolium chloride staining, immunohistochemistry, and immunofluorescent staining. Furthermore, treatment with Ast+Lig evidently prevented the upregulation of NR2B, but not NR2A, in vivo and in vitro following cerebral I\/R injury based on western blotting and reverse transcription\u2010quantitative PCR analyses. Moreover, treatment with Ast+Lig significantly increased the phosphorylation of ERK and CREB, as well as increasing their mRNA expression levels in vivo and in vitro following cerebral I\/R injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The overall results thus suggest that the Ast+Lig combination conferred neuroprotective properties against cerebral I\/R injury via regulation of the NR2B\u2010ERK\/CREB signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.2867","type":"journal-article","created":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T06:49:58Z","timestamp":1672469398000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The combination of\n                    <i>Astragalus membranaceus<\/i>\n                    and ligustrazine mitigates cerebral ischemia\u2010reperfusion injury via regulating NR2B\u2010ERK\/CREB signaling"],"prefix":"10.1002","volume":"13","author":[{"given":"Xialing","family":"Tang","sequence":"first","affiliation":[{"name":"The Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Diagnosis and Treatment Center of Encephalopathy Hubei Provincial Hospital of Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Xie","sequence":"additional","affiliation":[{"name":"The Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Diagnosis and Treatment Center of Encephalopathy Guangdong Provincial Hospital of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huajun","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Institute of Clinical Medicine Guangzhou 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