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Although immunometabolite S-2-hydroxyglutarate (S-2HG) is an emerging regulator of immune cells and thus triggers the immune response, it is unclear whether and how S-2HG elicits perioperative ischemic brain injury and exacerbates post-stroke cognitive dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Perioperative ischemic stroke was induced by transient middle cerebral artery occlusion for 60\u00a0min in C57BL\/6 mice 1\u00a0day after ileocecal resection. CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocyte activation and invasion of the cerebrovascular compartment were measured using flow cytometry. Untargeted metabolomic profiling was performed to detect metabolic changes in sorted CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes after ischemia. CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes were transfected with lentivirus ex vivo to mobilize cell proliferation and differentiation before being transferred into recombination activating gene 1 (Rag1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) stroke mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The perioperative stroke mice exhibit more severe cerebral ischemic injury and neurological dysfunction than the stroke-only mice. CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocyte invasion of brain parenchyma and neurotoxicity augment cerebral ischemic injury in the perioperative stroke mice. CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocyte depletion reverses exacerbated immune-mediated cerebral ischemic brain injury in perioperative stroke mice. Perioperative ischemic stroke triggers aberrant metabolic alterations in peripheral CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, in which S-2HG is more abundant. S-2HG alters CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocyte proliferation and differentiation ex vivo and modulates the immune-mediated ischemic brain injury and post-stroke cognitive dysfunction by enhancing CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocyte-mediated neurotoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study establishes that S-2HG signaling-mediated activation and neurotoxicity of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes might exacerbate perioperative ischemic brain injury and may represent a promising immunotherapy target in perioperative ischemic stroke.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-022-02537-4","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T17:03:18Z","timestamp":1657213398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The immunometabolite S-2-hydroxyglutarate exacerbates perioperative ischemic brain injury and cognitive dysfunction by enhancing CD8+ T lymphocyte-mediated neurotoxicity"],"prefix":"10.1186","volume":"19","author":[{"given":"Faqiang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaikai","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeguo","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"2537_CR1","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s12630-015-0494-9","volume":"63","author":"P Vlisides","year":"2016","unstructured":"Vlisides P, Mashour GA. 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