{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:21:20Z","timestamp":1787829680389,"version":"build-2784847793"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common and clinically significant perioperative neurocognitive disorders that disproportionately affect elderly surgical patients. Despite their substantial impact on postoperative recovery and long-term outcomes, the lack of validated biomarkers and effective targeted therapies remains a major challenge in perioperative medicine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Diagnostic Potential of Exosomes<\/jats:title>\n                    <jats:p>Owing to their intrinsic ability to cross the blood-brain barrier and stably encapsulate central nervous system-derived biomolecules, exosomes have emerged as promising candidates for non-invasive biomarker discovery in POD and POCD. Disease-associated alterations in exosomal cargo, encompassing proteins such as P-tau and A\u03b21-42, nucleic acids including miR-584\u20135p and circRNA_089763, and lipid-associated constituents, provide valuable molecular signatures for early diagnosis, disease stratification, prognostic assessment, and dynamic monitoring of perioperative neurocognitive disorders. It should be noted, however,that the majority of current evidence is extrapolated from Alzheimer\u2019s disease and other neurodegenerative conditions rather than directly validated in POD and POCD cohorts, and dedicated prospective studies remain warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Therapeutic Applications of Exosomes<\/jats:title>\n                    <jats:p>Exosomes exert therapeutic effects through two complementary mechanisms: serving as vehicles for targeted drug delivery and acting as endogenous neuroprotective mediators. Their excellent biocompatibility,low immunogenicity, and inherent capacity to traverse the blood-brain barrier render them attractive platforms for attenuating neuroinflammation, promoting synaptic repair, enhancing neurogenesis, and restoring blood-brain barrier integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Current Challenges and Future Perspectives<\/jats:title>\n                    <jats:p>Despite their considerable promise, several challenges continue to impede clinical translation, including limitations in large-scale production, the lack of standardized isolation and characterization protocols, biological heterogeneity, and regulatory barriers. Future research should focus on establishing POD\/POCD-specific exosomal biomarker panels, developing GMP-compliant manufacturing systems, engineering precision-targeted exosomal therapeutics, and conducting rigorous multicenter clinical studies to validate their safety and efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Exosomes hold substantial promise for transforming the diagnosis and treatment of POD and POCD. With continued advances in engineering technologies, mechanistic understanding, and clinical validation, exosome-based diagnostic and therapeutic strategies are expected to become an integral component of precision perioperative medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1854680","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:54:11Z","timestamp":1787036051000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exosomes: emerging biomarkers and therapeutic potential in postoperative delirium and postoperative cognitive dysfunction"],"prefix":"10.3389","volume":"14","author":[{"given":"Xinyu","family":"Li","sequence":"first","affiliation":[{"name":"The Second Clinical Medical School of Zhengzhou University","place":["Zhengzhou, Henan, China"]},{"name":"Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical School of Zhengzhou University","place":["Zhengzhou, Henan, China"]},{"name":"Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinjun","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","author":"Alvarez-Erviti","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1021\/acsnano.6b07607","article-title":"Re-Engineering extracellular vesicles as smart nanoscale therapeutics","volume":"11","author":"Armstrong","year":"2017","journal-title":"ACS Nano"},{"key":"B3","doi-asserted-by":"publisher","first-page":"6436","DOI":"10.26355\/eurrev_201810_16056","article-title":"Transplantation of human umbilical cord mesenchymal stem cells promotes functional recovery after spinal cord injury by blocking the expression of IL-7","volume":"22","author":"Bao","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2536","DOI":"10.1002\/stem.2412","article-title":"Mesenchymal stem cells are recruited and activated into carcinoma-associated fibroblasts by prostate cancer microenvironment-derived TGF-\u03b21","volume":"34","author":"Barcellos-de-Souza","year":"2016","journal-title":"Stem Cells"},{"key":"B5","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/s1474-4422(03)00530-1","article-title":"CSF markers for incipient alzheimer's disease","volume":"2","author":"Blennow","year":"2003","journal-title":"Lancet Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.1158\/1078-0432.CCR-17-3369","article-title":"Exosome-based detection of EGFR T790M in plasma from non-small cell lung cancer patients","volume":"24","author":"Castellanos-Rizaldos","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"7481","DOI":"10.1007\/s12035-024-04032-8","article-title":"Effects of bone marrow mesenchymal stem cell-derived exosomes in central nervous system diseases","volume":"61","author":"Chai","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4763","DOI":"10.2147\/JIR.S428425","article-title":"Mesenchymal stem cell transplantation: neuroprotection and nerve regeneration after spinal cord injury","volume":"16","author":"Chen","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.jprot.2015.12.023","article-title":"Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes","volume":"133","author":"Clark","year":"2016","journal-title":"J. Proteomics"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1097\/ALN.0b013e31821b1bc8","article-title":"Preoperative cognitive assessment of the elderly surgical patient: a call for action","volume":"114","author":"Crosby","year":"2011","journal-title":"Anesthesiology"},{"key":"B11","first-page":"767","article-title":"Research progress on exosomal RNA as diagnostic biomarkers for gastric cancer","volume":"22","author":"Deng","year":"2023","journal-title":"J. Difficult Complicat. Cases"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.5966\/sctm.2015-0078","article-title":"Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression","volume":"4","author":"Doeppner","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"625659","DOI":"10.1155\/2015\/625659","article-title":"Serum MicroRNA profiles serve as novel biomarkers for the diagnosis of alzheimer's disease","volume":"2015","author":"Dong","year":"2015","journal-title":"Dis. Markers"},{"key":"B14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.2147\/DNND.S444567","article-title":"Serum exosomal miRNA-125b and miRNA-451a are potential diagnostic biomarker for Alzheimer's diseases","volume":"14","author":"Duan","year":"2024","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"S81","DOI":"10.1053\/j.seminoncol.2005.03.014","article-title":"Non-small cell lung cancer treatment-related bone marrow toxicities","volume":"32","author":"Ettinger","year":"2005","journal-title":"Semin. Oncol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/JAD-189004","article-title":"Recommendations for the nomenclature of cognitive change associated with anaesthesia and Surgery-20181","volume":"66","author":"Evered","year":"","journal-title":"J. Alzheimers Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1097\/ALN.0000000000002334","article-title":"Recommendations for the nomenclature of cognitive change associated with anaesthesia and Surgery-2018","volume":"129","author":"Evered","year":"","journal-title":"Anesthesiology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e14719","DOI":"10.1111\/cns.14719","article-title":"Mesenchymal stem cell-derived exosomes improve neurogenesis and cognitive function of mice with methamphetamine addiction: a novel treatment approach","volume":"30","author":"Fallahi","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0275917","DOI":"10.1371\/journal.pone.0275917","article-title":"Plasma microRNA-221-3p as a biomarker for POCD after non-cardiac surgery","volume":"17","author":"Fan","year":"2022","journal-title":"PLoS One"},{"key":"B20","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.mcn.2005.12.003","article-title":"Exosomes are released by cultured cortical neurones","volume":"31","author":"Faur\u00e9","year":"2006","journal-title":"Mol. Cell Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.jalz.2014.06.008","article-title":"Identification of preclinical alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case-control study","volume":"11","author":"Fiandaca","year":"2015","journal-title":"Alzheimers Dement."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1001\/jamasurg.2015.2606","article-title":"Effect of delirium and other major complications on outcomes after elective surgery in older adults","volume":"150","author":"Gleason","year":"2015","journal-title":"JAMA Surg."},{"key":"B23","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/978-1-4939-3584-0_7","article-title":"Paracrine mechanisms of mesenchymal stem cells in tissue repair","volume":"1416","author":"Gnecchi","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1212\/WNL.0000000000001702","article-title":"Altered lysosomal proteins in neural-derived plasma exosomes in preclinical alzheimer disease","volume":"85","author":"Goetzl","year":"2015","journal-title":"Neurology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4141","DOI":"10.1096\/fj.201600816R","article-title":"Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and alzheimer's disease","volume":"30","author":"Goetzl","year":"2016","journal-title":"FASEB J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1096\/fj.201700731R","article-title":"Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of alzheimer's disease","volume":"32","author":"Goetzl","year":"2018","journal-title":"FASEB J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"9195","DOI":"10.1093\/nar\/gku594","article-title":"Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons","volume":"42","author":"Goldie","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B28","article-title":"Research on the role of downregulation of the cholinergic anti-inflammatory pathway in early postoperative cognitive dysfunction (POCD) in aged mice thesis","author":"Gong","year":"2020"},{"key":"B29","doi-asserted-by":"publisher","first-page":"102223","DOI":"10.1016\/j.arr.2024.102223","article-title":"Unveiling the role of astrocytes in postoperative cognitive dysfunction","volume":"95","author":"He","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.cell.2020.07.009","article-title":"Extracellular vesicle and particle biomarkers define multiple human cancers","volume":"182","author":"Hoshino","year":"2020","journal-title":"Cell"},{"key":"B31","first-page":"2006","article-title":"Research progress on exosomes in pulmonary diseases","volume":"39","author":"Huang","year":"2023","journal-title":"Chin. Pharmacol. Bull"},{"key":"B32","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41467-018-02989-4","article-title":"Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity","volume":"9","author":"Janas","year":"2018","journal-title":"Nat. Commun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"5548630","DOI":"10.1155\/2021\/5548630","article-title":"Extracellular vesicles released from neprilysin gene-modified human umbilical cord-derived mesenchymal stem cell enhance therapeutic effects in an alzheimer's disease animal model","volume":"2021","author":"Jeong","year":"2021","journal-title":"Stem Cells Int."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/j.jalz.2019.05.002","article-title":"Concordance between the assessment of A\u03b242, T-tau, and P-T181-tau in peripheral blood neuronal-derived exosomes and cerebrospinal fluid","volume":"15","author":"Jia","year":"2019","journal-title":"Alzheimers Dement."},{"key":"B35","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1097\/YCO.0000000000000842","article-title":"Exosomes for the diagnosis and treatment of dementia","volume":"36","author":"Joo","year":"2023","journal-title":"Curr. Opin. Psychiatry"},{"key":"B36","doi-asserted-by":"publisher","first-page":"6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1172\/JCI81135","article-title":"The biology and function of exosomes in cancer","volume":"126","author":"Kalluri","year":"2016","journal-title":"J. Clin. Invest"},{"key":"B38","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1038\/mt.2010.27","article-title":"Targeted delivery of siRNA to macrophages for anti-inflammatory treatment","volume":"18","author":"Kim","year":"2010","journal-title":"Mol. Ther."},{"key":"B39","doi-asserted-by":"publisher","first-page":"609","DOI":"10.4103\/1673-5374.350205","article-title":"Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes","volume":"18","author":"Lang","year":"2023","journal-title":"Neural Regen. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"30087","DOI":"10.3402\/jev.v4.30087","article-title":"Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper","volume":"4","author":"Lener","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"B41","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12943-024-02215-4","article-title":"Emerging role of exosomes in cancer therapy: progress and challenges","volume":"24","author":"Li","year":"2025","journal-title":"Mol. Cancer"},{"key":"B42","doi-asserted-by":"publisher","first-page":"115582","DOI":"10.1016\/j.biopha.2023.115582","article-title":"Neuroinflammation: the central enabler of postoperative cognitive dysfunction","volume":"167","author":"Liu","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B43","doi-asserted-by":"publisher","first-page":"4134","DOI":"10.1158\/0008-5472.CAN-08-4698","article-title":"Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer","volume":"69","author":"Loebinger","year":"2009","journal-title":"Cancer Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s10571-015-0314-3","article-title":"Schwann cell exosomes mediate neuron-glia communication and enhance axonal regeneration","volume":"36","author":"Lopez-Leal","year":"2016","journal-title":"Cell Mol. Neurobiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"4853","DOI":"10.1113\/JP282799","article-title":"Exosome engineering for efficient and targeted drug delivery: current status and future perspective","volume":"601","author":"Malekian","year":"2023","journal-title":"J. Physiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1016\/j.jprot.2010.06.006","article-title":"Exosomes: extracellular organelles important in intercellular communication","volume":"73","author":"Mathivanan","year":"2010","journal-title":"J. Proteomics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1186\/s12871-024-02722-3","article-title":"The association of pre-operative biomarkers of endothelial dysfunction with the risk of post-operative neurocognitive disorders: results from the BioCog study","volume":"24","author":"Moazzen","year":"2024","journal-title":"BMC Anesthesiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/s0140-6736(97)07382-0","article-title":"Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International study of post-operative cognitive dysfunction","volume":"351","author":"Moller","year":"1998","journal-title":"Lancet"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.jconrel.2022.12.027","article-title":"Hybrid exosomes, exosome-like nanovesicles and engineered exosomes for therapeutic applications","volume":"353","author":"Mondal","year":"2023","journal-title":"J. Control Release"},{"key":"B50","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/nature25456","article-title":"High performance plasma amyloid-\u03b2 biomarkers for alzheimer's disease","volume":"554","author":"Nakamura","year":"2018","journal-title":"Nature"},{"key":"B51","doi-asserted-by":"publisher","first-page":"i115","DOI":"10.1093\/bja\/aex354","article-title":"Postoperative cognitive dysfunction and dementia: what we need to know and do","volume":"119","author":"Needham","year":"2017","journal-title":"Br. J. Anaesth."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.27288\/d.cnki.gsxyu.2021.000012","article-title":"Research on the therapeutic effects and mechanisms of human mesenchymal stem cell-derived exosomes on hippocampal neurogenesis and in animal models of alzheimer's disease dissertation","author":"Niu","year":"2021","journal-title":"Taiyuan"},{"key":"B53","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/s41592-021-01174-8","article-title":"L1CAM is not associated with extracellular vesicles in human cerebrospinal fluid or plasma","volume":"18","author":"Norman","year":"2021","journal-title":"Nat. Methods"},{"key":"B54","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1177\/0271678X17708917","article-title":"Exosomes promote restoration after an experimental animal model of intracerebral hemorrhage","volume":"38","author":"Otero-Ortega","year":"2018","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"B55","doi-asserted-by":"publisher","first-page":"920686","DOI":"10.3389\/fncel.2022.920686","article-title":"Neuroprotective and neurotoxic effects of glial-derived exosomes","volume":"16","author":"Oyarce","year":"2022","journal-title":"Front. Cell Neurosci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"573","DOI":"10.2147\/JIR.S349572","article-title":"Regulatory role of mesenchymal stem cells on secondary inflammation in spinal cord injury","volume":"15","author":"Pang","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3233\/JAD-2012-112192","article-title":"Intrahippocampal administration of amyloid-\u03b21-42 oligomers acutely impairs spatial working memory, insulin signaling, and hippocampal metabolism","volume":"30","author":"Pearson-Leary","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"B58","doi-asserted-by":"publisher","first-page":"111474","DOI":"10.1016\/j.yexcr.2019.06.019","article-title":"Astrocyte-derived exosomes suppress autophagy and ameliorate neuronal damage in experimental ischemic stroke","volume":"382","author":"Pei","year":"2019","journal-title":"Exp. Cell Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1096\/fj.08-122424","article-title":"Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia","volume":"23","author":"Planel","year":"2009","journal-title":"FASEB J."},{"key":"B60","doi-asserted-by":"publisher","first-page":"578403","DOI":"10.1016\/j.jneuroim.2024.578403","article-title":"Macrophage-derived exosomes exacerbate postoperative cognitive dysfunction in mice through inflammation","volume":"394","author":"Qin","year":"2024","journal-title":"J. Neuroimmunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"730","DOI":"10.3390\/mi13050730","article-title":"Microfluidic platforms for the isolation and detection of exosomes: a brief review","volume":"13","author":"Raju","year":"2022","journal-title":"Micromachines (Basel)"},{"key":"B62","doi-asserted-by":"publisher","first-page":"752","DOI":"10.3389\/fpsyt.2018.00752","article-title":"The role of neuroinflammation in postoperative cognitive dysfunction: moving from hypothesis to treatment","volume":"9","author":"Safavynia","year":"2019","journal-title":"Front. Psychiatry"},{"key":"B63","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3389\/fnins.2017.00082","article-title":"Exosomes: origins and therapeutic potential for neurodegenerative disease","volume":"11","author":"Sarko","year":"2017","journal-title":"Front. Neurosci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1038\/nm1782","article-title":"Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory","volume":"14","author":"Shankar","year":"2008","journal-title":"Nat. Med."},{"key":"B65","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/s41556-025-01682-1","article-title":"Extracellular exosomal RNAs are glyco-modified","volume":"27","author":"Sharma","year":"2025","journal-title":"Nat. Cell Biol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s00401-014-1314-y","article-title":"Plasma exosomal \u03b1-synuclein is likely CNS-Derived and increased in parkinson's disease","volume":"128","author":"Shi","year":"2014","journal-title":"Acta Neuropathol."},{"key":"B67","first-page":"108","article-title":"Lik sprava","author":"Sivak","year":"2015"},{"key":"B68","doi-asserted-by":"publisher","first-page":"e0195969","DOI":"10.1371\/journal.pone.0195969","article-title":"Identification of RNA-Binding proteins in exosomes capable of interacting with different types of RNA: RBP-Facilitated transport of RNAs into exosomes","volume":"13","author":"Statello","year":"2018","journal-title":"PLoS One"},{"key":"B69","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41580-020-00315-9","article-title":"Gene regulation by long non-coding RNAs and its biological functions","volume":"22","author":"Statello","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1002\/ana.22664","article-title":"Resolving postoperative neuroinflammation and cognitive decline","volume":"70","author":"Terrando","year":"2011","journal-title":"Ann. Neurol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/nri2395","article-title":"Mesenchymal stem cells in health and disease","volume":"8","author":"Uccelli","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.jconrel.2020.04.017","article-title":"Astrocyte-derived extracellular vesicles: neuroreparative properties and role in the pathogenesis of neurodegenerative disorders","volume":"323","author":"Upadhya","year":"2020","journal-title":"J. Control Release"},{"key":"B73","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.addr.2012.06.011","article-title":"Exosomes as nucleic acid nanocarriers","volume":"65","author":"van den Boorn","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B75","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"van Niel","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"17","DOI":"10.16505\/j.2095-0136.2016.01.004","article-title":"Isolation of exosomal HCV RNA from cell culture supernatant of HCV subgenomic replicon cells and its correlation with intracellular viral levels","volume":"6","author":"Wang","year":"2016","journal-title":"Chin. J. Viral Dis."},{"key":"B77","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.3892\/mmr.2019.10521","article-title":"Abnormal expression of circRNA_089763 in the plasma exosomes of patients with post-operative cognitive dysfunction after coronary artery bypass grafting","volume":"20","author":"Wang","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B78","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.jconrel.2020.10.020","article-title":"Challenges in the development and establishment of exosome-based drug delivery systems","volume":"329","author":"Wang","year":"2021","journal-title":"J. Control Release"},{"key":"B79","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s10020-023-00727-1","article-title":"Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1\/miR-382-3p\/BDNF signaling pathway in serum-exosomes","volume":"29","author":"Wang","year":"2023","journal-title":"Mol. Med."},{"key":"B80","doi-asserted-by":"publisher","first-page":"8603","DOI":"10.2147\/IJN.S218988","article-title":"A nanodrug consisting of doxorubicin and exosome derived from mesenchymal stem cells for osteosarcoma treatment in vitro","volume":"14","author":"Wei","year":"2019","journal-title":"Int. J. Nanomedicine"},{"key":"B81","doi-asserted-by":"publisher","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"B82","doi-asserted-by":"publisher","first-page":"eaav8521","DOI":"10.1126\/scitranslmed.aav8521","article-title":"Advances in therapeutic applications of extracellular vesicles","volume":"11","author":"Wiklander","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"B83","doi-asserted-by":"publisher","first-page":"738","DOI":"10.3389\/fimmu.2018.00738","article-title":"Extracellular vesicle heterogeneity: subpopulations, isolation techniques, and diverse functions in cancer progression","volume":"9","author":"Willms","year":"2018","journal-title":"Front. Immunol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.2147\/NDT.S374722","article-title":"Association plasma A\u03b242 levels with alzheimer's disease and its influencing factors in Chinese elderly population","volume":"18","author":"Wu","year":"2022","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"B85","doi-asserted-by":"publisher","first-page":"e3281","DOI":"10.1002\/brb3.3281","article-title":"Relationship between preoperative neutrophil-to-lymphocyte ratio and postoperative delirium: the PNDABLE and the PNDRFAP cohort studies","volume":"13","author":"Wu","year":"2023","journal-title":"Brain Behav."},{"key":"B86","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1097\/00000542-200605000-00015","article-title":"The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels","volume":"104","author":"Xie","year":"2006","journal-title":"Anesthesiology"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1038\/jcbfm.2013.152","article-title":"Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats","volume":"33","author":"Xin","year":"2013","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"B88","doi-asserted-by":"publisher","first-page":"102309","DOI":"10.1016\/j.jchemneu.2023.102309","article-title":"Exosome-shuttled MYCBPAP from bone marrow mesenchymal stem cells regulates synaptic remodeling and ameliorates ischemic stroke in rats","volume":"132","author":"Yan","year":"2023","journal-title":"J. Chem. Neuroanat."},{"key":"B89","doi-asserted-by":"publisher","first-page":"29466","DOI":"10.1038\/s41598-024-80865-6","article-title":"Exploring molecular mechanisms of postoperative delirium through multi-omics strategies in plasma exosomes","volume":"14","author":"Yan","year":"2024","journal-title":"Sci. Rep."},{"key":"B90","doi-asserted-by":"publisher","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Y\u00e1\u00f1ez-M\u00f3","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"B91","doi-asserted-by":"publisher","first-page":"2134565","DOI":"10.1155\/2020\/2134565","article-title":"Exosomes of antler mesenchymal stem cells improve postoperative cognitive dysfunction in cardiopulmonary bypass rats through inhibiting the TLR2\/TLR4 signaling pathway","volume":"2020","author":"Yang","year":"2020","journal-title":"Stem Cells Int."},{"key":"B92","doi-asserted-by":"publisher","first-page":"137010","DOI":"10.1016\/j.neulet.2022.137010","article-title":"Elevated complement component 8 gamma levels in astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea patients without dementia","volume":"794","author":"Yang","year":"2023","journal-title":"Neurosci. Lett."},{"key":"B93","article-title":"Research on exosomal lncRNAs as biomarkers for colorectal cancer dissertation","author":"Yu","year":"2022"},{"key":"B94","first-page":"423","article-title":"Clinical significance of exosomal long noncoding RNA DANCR as a novel serum-based diagnostic and prognostic biomarker in osteosarcoma","volume":"12","author":"Yuan","year":"2019","journal-title":"Int. J. Clin. Exp. Med."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1111\/nicc.13081","article-title":"Associations between postoperative cognitive dysfunction, serum interleukin-6 and postoperative delirium among patients after coronary artery bypass grafting: a mediation analysis","volume":"29","author":"Zhang","year":"2024","journal-title":"Nurs. Crit. Care"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1016\/j.cmet.2025.04.009","article-title":"The foam cell-derived exosomes exacerbate ischemic white matter injury via transmitting metabolic defects to microglia","volume":"37","author":"Zhang","year":"","journal-title":"Cell Metab."},{"key":"B97","doi-asserted-by":"publisher","first-page":"189300","DOI":"10.1016\/j.bbcan.2025.189300","article-title":"Exosomes: traversing the blood-brain barrier and their therapeutic potential in brain cancer","volume":"1880","author":"Zhang","year":"","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.21037\/atm-21-6086","article-title":"Exosomal miRNA-223-3p as potential biomarkers in patients with cerebral small vessel disease cognitive impairment","volume":"9","author":"Zhao","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"B99","doi-asserted-by":"publisher","first-page":"9890","DOI":"10.18632\/aging.204398","article-title":"Sevoflurane-induced POCD-Associated exosomes delivered miR-584-5p regulates the growth of human microglia HMC3 cells through targeting BDNF","volume":"14","author":"Zhao","year":"2022","journal-title":"Aging (Albany NY)"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1854680\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:51:57Z","timestamp":1787827917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1854680\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":99,"alternative-id":["10.3389\/fcell.2026.1854680"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1854680","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"article-number":"1854680"}}