{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:28:47Z","timestamp":1793579327456,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100124"],"award-info":[{"award-number":["82100124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571561"],"award-info":[{"award-number":["82571561"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The brain\u2010derived neurotrophic factor (BDNF) is a potent neuroprotective factor; however, its large molecular size limits its ability to cross structural barriers such as the blood\u2013spinal cord barrier. This study explores the therapeutic potential of exosome\u2010mediated delivery of engineered circular BDNF (circBDNF) to promote spinal cord injury (SCI) repair through activation of the PI3K\/AKT\/mTOR signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A synthetic circBDNF sequence encoding BDNF was used to construct a circBDNF overexpression plasmid, which was transfected into HEK293T cells to generate circBDNF\u2010loaded exosomes (circBDNF\u2010EXO). These exosomes were characterized via transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. In\u00a0vitro, the protective effects of circBDNF\u2010EXO were evaluated in an oxygen\u2013glucose deprivation\/reperfusion (OGD) injury model in HT22 cells, focusing on cell viability, reactive oxygen species (ROS) levels, apoptosis, inflammation, and signaling pathways. In\u00a0vivo, a T10 SCI mouse model was employed to assess therapeutic efficacy, using behavioral, electrophysiological, histological, and molecular analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vitro, circBDNF\u2010EXO treatment significantly increased BDNF expression, enhanced cell viability, reduced ROS levels, mitigated inflammation, and inhibited apoptosis in HT22 cells following OGD injury. In\u00a0vivo, administration of circBDNF\u2010EXO resulted in improved motor function recovery, evidenced by increased Basso Mouse Scale scores, enhanced gait coordination, and better motor\u2010evoked potentials. Histological analyses demonstrated elevated BDNF expression, decreased apoptosis, reduced oxidative stress, and enhanced axonal regeneration in the injured spinal cord. Mechanistically, circBDNF\u2010EXO activated TrkB receptors and upregulated the PI3K\/AKT\/mTOR signaling pathway, as confirmed by Western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Exosome\u2010mediated delivery of circBDNF promotes SCI repair by activating the PI3K\/AKT\/mTOR pathway, suppressing apoptosis, oxidative stress, and inflammation, and enhancing axonal regeneration. This innovative approach holds substantial promise for SCI treatment and deserves further exploration in preclinical and clinical studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70784","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T04:15:57Z","timestamp":1773980157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exosome\u2010Loaded Engineered\n                    <scp>circBDNF<\/scp>\n                    Promotes Spinal Cord Injury Repair Through the\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>mTOR<\/scp>\n                    Signaling Axis"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-7446","authenticated-orcid":false,"given":"Gang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei Province China"},{"name":"Department of Spinal Surgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong Province China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganggang","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Spinal Surgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong Province China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Gu","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou Guangdong China"},{"name":"Department of Joint Surgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Spinal Surgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong Province China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1008-8072","authenticated-orcid":false,"given":"Yong","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Spinal Surgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong Province China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0684-5341","authenticated-orcid":false,"given":"Baoshu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong Province People's Republic of 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