{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:01:54Z","timestamp":1790812914867,"version":"4.1.0"},"reference-count":35,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"The Institutes of Brain Science,Wannan Medical College","award":["KF2024010"],"award-info":[{"award-number":["KF2024010"]}]},{"name":"The Scientific Research Program of Anhui Province","award":["2022AH010073"],"award-info":[{"award-number":["2022AH010073"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Stroke Vasc Neurol"],"accepted":{"date-parts":[[2025,8,22]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Subarachnoid haemorrhage (SAH) is primarily caused by ruptured aneurysms with high mortality worldwide. Cuproptosis is a copper-induced cell death that regulates lipoylated tricarboxylic acid cycle proteins. The link between cuproptosis and SAH is unclear. To inhibit cuproptosis for SAH treatment, we designed brain-targeted delivery of siRNA to inhibit cuproptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptome data of SAH related to cuprotosis were extracted from the Gene Expression Omnibus and defined using quantitative reverse transcription-PCR. We injected RVG-RBCEVs\/siRNA (rabies virus glycoprotein-red blood cell extracellular vesicles\/siRNA) peripherally to deliver LIAS (lipoyl synthase) siRNA to the brain tissues of SAH mice. The influences of RVG-RBCEVs\/siRNA on copper levels, enrichment of cuproptosis functional proteins, glutathione and malondialdehyde content, mitochondrial respiration and membrane potential, transmission electron microscope, a neurological score, brain water content, blood\u2013brain barrier injury and Fluoro-Jade C staining were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed that three cuproptosis-related genes (CRGs) were differentially expressed. The RVG peptides were conjugated to the red blood cell extracellular vesicle surface by bio-orthogonal click chemistry reactions, and then the loading of siRNA was conducted. RVG-RBCEVs\/siRNA was selectively taken up by neurons but not glial cells; it facilitated the downregulation of LIAS of CRGs, reduced the accumulation of reactive oxygen species, inhibited neuronal cuprotosis and exerted neuroprotective effects in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that cuprotosis is critical for inducing neural injury after SAH. Neuron-targeted RVG-RBCEVs\/siRNA treatment attenuated oxidative stress by inhibiting cuproptosis via suppressed LIAS expression. This innovative approach alleviates neurobehavioural impairments and represents a neuroprotective strategy following SAH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/svn-2025-004248","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T09:10:11Z","timestamp":1757927411000},"page":"227-239","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Brain-targeted extracellular vesicles for anti-cuproptosis therapy in subarachnoid haemorrhage"],"prefix":"10.1136","volume":"11","author":[{"given":"Pengcheng","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), The Translational Research Institute for Neurological Disorders of Wannan Medical College, Wuhu, Anhui, China"},{"name":"The Institutes of Brain Science, Wannan Medical College, Wuhu, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), The Translational Research Institute for Neurological Disorders of Wannan Medical College, Wuhu, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyun","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), The Translational Research Institute for Neurological Disorders of Wannan Medical College, Wuhu, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayong","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), The Translational Research Institute for Neurological Disorders of Wannan Medical College, Wuhu, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), The Translational Research Institute for Neurological Disorders of Wannan Medical College, Wuhu, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), The Translational Research Institute for Neurological Disorders of Wannan Medical College, Wuhu, Anhui, China"},{"name":"The Institutes of Brain Science, Wannan Medical College, Wuhu, Anhui, 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