{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:20:28Z","timestamp":1787502028280,"version":"build-2736575974"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,5,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Lyn kinase is a member of the Src family of tyrosine kinases, primarily known for its role in regulating immune cell signaling. It can phosphorylate and modulate the activity of various proteins involved in immune responses, including Toll\u2010like receptor 4 (\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">TLR4)<\/jats:styled-content>\n                      .\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">TLR4<\/jats:styled-content>\n                      \u2010mediated inflammatory pathways have been extensively studied; however, the sex\u2010specific interaction of\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">TLR4<\/jats:styled-content>\n                      and Lyn in neuroinflammation after aneurysmal subarachnoid hemorrhage (\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">SAH<\/jats:styled-content>\n                      ) has yet to be investigated.\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">SAH<\/jats:styled-content>\n                      occurs due to a ruptured aneurysm, and the consequences often lead to neuroinflammation and cognitive impairments. In our study, we investigated the sex\u2010specific involvement of Lyn kinase in regulating\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">TLR4<\/jats:styled-content>\n                      signaling to understand the\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">TLR4<\/jats:styled-content>\n                      \u2010mediated inflammatory response after\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">SAH<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Cell\u2010specific Lyn knockout mice of both sexes were used for this study. Wild\u2010type and conditional knockout mouse brains were analyzed by multicolor flow cytometry, immunohistochemistry, and western blotting at postoperative day 7 following\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">SAH<\/jats:styled-content>\n                      surgery. An unbiased spatial transcriptomic analysis was performed with the frozen mouse brain tissues. A\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">3\u2010dimensional<\/jats:styled-content>\n                      brain stroke model and\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">cerebrospinal fluid<\/jats:styled-content>\n                      samples\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">of<\/jats:styled-content>\n                      patients with\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">SAH<\/jats:styled-content>\n                      were also used for this study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Our overall animal and patient data from flow cytometry, immunohistochemistry, western blot, cognitive function tests, and spatial transcriptomic data revealed that Lyn kinase is a sex\u2010specific regulator in inflammatory cytokine production, red blood cell phagocytosis, neuronal apoptosis, and cognitive function, as well as a negative regulator of\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">TLR4<\/jats:styled-content>\n                      signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Our results highlight sex\u2010specific modulation of Lyn kinase activity in\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">TLR4<\/jats:styled-content>\n                      signaling after hemorrhagic stroke and indicate that successful treatment of neuroinflammation may require sex\u2010specific treatments.\n                    <\/jats:p>\n             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