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Cell. Neurosci."],"abstract":"<jats:p>Spinal cord injury (SCI) is a devastating disorder of the central nervous system. It is characterized by primary mechanical damage and secondary pathological cascades. These lead to persistent sensory and motor deficits, substantial socioeconomic burdens, and limited therapeutic efficacy. Exosomes are nanoscale vesicles secreted by various cells that serve as key mediators of intercellular communication by delivering bioactive molecules, particularly microRNAs (miRNAs), which regulate gene expression in target cells. This review explores how exosomal miRNAs contribute to neural repair in SCI. These contributions include inhibiting neuroinflammation via pathways such as NF-\u03baB and TLR4; suppressing neuronal apoptosis through PTEN\/PI3K\/Akt signaling; promoting axonal regeneration via the ERK1\/2\/STAT3 and NGF\/TrkA pathways, enhancing angiogenesis by targeting SPRED1 and integrin \u03b15, and modulating of the immune microenvironment toward M2 polarization, and multifaceted neuroprotection involving alleviating autophagy and endoplasmic reticulum stress. Drawing on recent preclinical studies from 2024\u20132025, including those utilizing mesenchymal stem cell\u2013derived exosomes loaded with miRNAs such as miR-124-3p, miR-338-5p, and miR-216a-5p, the review highlights promising innovations, such as bioengineered exosomes and biomaterial integrations. Recent preclinical advancements, such as exosome-based therapies that have shown reduced lesion volumes and improved motor function in rodent models, highlight the potential for translation to clinical applications. Ongoing efforts are anticipated to lead to clinical trials in the near future. Despite challenges in standardization, delivery efficiency, immunogenicity, and long-term safety, exosomal miRNA therapy offers a cell-free, multitargeted approach with strong potential for clinical translation in SCI management.<\/jats:p>","DOI":"10.3389\/fncel.2025.1711454","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T07:02:31Z","timestamp":1768892551000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The potential mechanisms and regulatory roles of exosomal miRNA in neural repair after spinal cord injury"],"prefix":"10.3389","volume":"19","author":[{"given":"Yuanhu","family":"Shi","sequence":"first","affiliation":[{"name":"School of Medicine and Affiliated Nantong Hospital 3 of Nantong University","place":["Nantong, Jiangsu, China"]},{"name":"School of Medicine, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine and Affiliated Nantong Hospital 3 of Nantong University","place":["Nantong, Jiangsu, China"]},{"name":"School of Medicine, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxu","family":"Pu","sequence":"additional","affiliation":[{"name":"School of Medicine, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Nantong City No.1 People's Hospital and The Affiliated Hospital 2 of Nantong University and Research Institute for Spine and Spinal Cord Disease of Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longju","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Science and Education in Affiliated Nantong Hospital 3 of Nantong University and Nantong Third People's Hospital","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopedics in Affiliated Nantong Hospital 3 of Nantong University","place":["Nantong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1093\/neuros\/nyw080","article-title":"Traumatic spinal cord injury-repair and regeneration","volume":"80","author":"Ahuja","year":"2017","journal-title":"Neurosurgery"},{"key":"B2","doi-asserted-by":"publisher","first-page":"282","DOI":"10.3389\/fneur.2019.00282","article-title":"Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms","volume":"10","author":"Alizadeh","year":"2019","journal-title":"Front. 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