{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:48:54Z","timestamp":1792716534002,"version":"4.5.0"},"reference-count":70,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Previous studies have reported the presence of interferon\u2010responsive microglia in the brain after central nervous system injury. However, their roles and the underlying mechanisms in neurological function recovery remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Adult male mice were subjected to 90\u2010minute transient middle cerebral artery occlusion, and brain tissues were analyzed using single\u2010cell RNA sequencing (scRNA\u2010seq) at 14\u2009days after stroke. Immunostaining, quantitative real\u2010time polymerase chain reaction and ELISA were conducted to validate the presence of interferon\u2010\u03b3\u2013responsive microglia in stroke mice brains. Extracellular vesicles (EVs) were isolated from interferon\u2010\u03b3\u2013treated BV2 microglia via ultracentrifugation. Interferon\u2010\u03b3 EVs were then used to treat neural stem cells (NSCs) in\u00a0vitro or administered intravenously to mice every other day, starting at 7\u2009days after transient middle cerebral artery occlusion. Neurobehavioral tests, cresyl violet staining, Golgi staining, and immunostaining were performed to evaluate NSC differentiation, neurogenesis, and neurobehavioral recovery. Micro RNA (miR) sequencing and bioinformatic analysis were conducted to explore targeted genes and signaling pathways underlying interferon\u2010\u03b3 EV\u2010mediated inhibition of neurogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Single\u2010cell RNA sequencing, immunostaining, quantitative real\u2010time polymerase chain reaction, and ELISA showed the presence of interferon\u2010\u03b3\u2013responsive microglia in stroke mice brains. Interferon\u2010\u03b3 EVs were internalized by NSCs, leading to reduced NSC survival and neuronal differentiation. Administration of interferon\u2010\u03b3 EVs increased brain atrophy volume, inhibited neurobehavioral recovery and neurogenesis in mice after stroke. miRNA array revealed 12 upregulated microRNAs, and treatment with miR\u2010199a\u20105p mimic inhibited the survival and neuronal differentiation of NSCs, and knockdown of miR\u2010199a\u20105p in interferon\u2010\u03b3 EVs increased neurogenesis in stroke mice. miRNA database analysis and luciferase reporter assay identified\n                      <jats:italic toggle=\"no\">SIRT1<\/jats:italic>\n                      as a downstream target gene of miR\u2010199a\u20105p. Treatment with SIRT1 agonist promoted the survival and neuronal differentiation of NSCs, confirming that interferon\u2010\u03b3 EVs inhibited neurogenesis via miR\u2010199a\u20105p\/\n                      <jats:italic toggle=\"no\">SIRT1<\/jats:italic>\n                      .\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 study demonstrated that interferon\u2010\u03b3 EVs inhibited the survival and neuronal differentiation of NSCs, exacerbating brain injury via the miR\u2010199a\u20105p\/\n                      <jats:italic toggle=\"no\">SIRT1<\/jats:italic>\n                      axis after ischemic stroke, providing a novel target for treating ischemic stroke.\n                    <\/jats:p>\n                  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