{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:28:44Z","timestamp":1789939724784,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071351"],"award-info":[{"award-number":["82071351"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Cellular prion protein (PrP<jats:sup>C<\/jats:sup>), the primary form of prion diseases pathogen, has received increasing attention for its protective effect against ischaemic stroke. Little is known about its role in peripheral immune responses after cerebral ischaemia\/reperfusion (I\/R) injury. This study is to detect the variation of splenic CD4<jats:sup>+<\/jats:sup> T lymphocytes differentiation and the concentration of inflammatory cytokines after murine cerebral I\/R injury in the context of <jats:italic>PRNP<\/jats:italic> expression as well as its influence on the ischaemic neuronal apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established the cerebral ischaemic murine model of different <jats:italic>PRNP<\/jats:italic> genotypes. We detected the percentage of splenic CD4<jats:sup>+<\/jats:sup>PrP<jats:sup>C+<\/jats:sup> T cells of <jats:italic>PRNP<\/jats:italic> wild\u2010type mice and the ratio of splenic Th1\/2\/17 lymphocytes of mice of different PRNP expression. The relevant inflammatory cytokines were then measured. Oxygen glucose deprivation\/reperfusion (OGD\/R) HT22 mouse hippocampal neurons were co\u2010cultured with the T\u2010cell\u2010conditioned medium harvested from the spleen of modelled mice and then the neuronal apoptosis was detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CD4<jats:sup>+<\/jats:sup> PrP<jats:sup>C+<\/jats:sup> T lymphocytes in wild\u2010type mice elevated after MCAO\/R. <jats:italic>PRNP<\/jats:italic> expression deficiency led to an elevation of Th1\/17 phenotypes and the promotion of pro\u2010inflammatory cytokines, while <jats:italic>PRNP<\/jats:italic> overexpression led to the elevation of Th2 phenotype and upregulation of anti\u2010inflammatory cytokines. In addition, PrP<jats:sup>C<\/jats:sup>\u2010overexpressed CD4<jats:sup>+<\/jats:sup>T cells weakened the apoptosis of OGD\/R HT\u201022 murine hippocampal neurons caused by MCAO\/R CD4<jats:sup>+<\/jats:sup> T\u2010cell\u2010conditioned medium, while PrP<jats:sup>C<\/jats:sup> deficiency enhanced apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>PrP<jats:sup>C<\/jats:sup> works as a neuron protector in the CNS when I\/R injury occurs and affects the peripheral immune responses and defends against stroke\u2010induced neuronal apoptosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51453","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:46:53Z","timestamp":1631710013000},"page":"2040-2051","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Role of cellular prion protein in splenic CD4<sup>+<\/sup> T cell differentiation in cerebral ischaemic\/reperfusion"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-5598","authenticated-orcid":false,"given":"Baizhuo","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology Neuroscience Center The First Hospital of Jilin University Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Neurology Neuroscience Center The First Hospital of Jilin University Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Neurology Neuroscience Center The First Hospital of Jilin University Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2340-3526","authenticated-orcid":false,"given":"Xiaoou","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology Neuroscience Center The First Hospital of Jilin University Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Neurology Neuroscience Center The First Hospital of Jilin University Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Neurology Neuroscience Center The First Hospital of Jilin University Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4254-6736","authenticated-orcid":false,"given":"Li","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurology Neuroscience Center The First Hospital of Jilin University Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.25.7.1481"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1995.18"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.1.155"},{"key":"e_1_2_8_5_1","first-page":"1","article-title":"Post\u2010ischemic inflammation regulates neural damage and protection","volume":"8","author":"Yoshimura A","year":"2014","journal-title":"Front 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