{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T06:31:40Z","timestamp":1765780300323,"version":"3.48.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"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. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) on extrapyramidal neural network of Wilson disease (WD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      27 6-month-old toxic milk mice (TX mice, WD animal model) and 15 C57 mice were selected. Corrected phase (CP) value on susceptibility weighted imaging (SWI), fractional anisotropy (FA) on diffusion tensor imaging (DTI) were performed. The volume of fiber connections was determined. BMSCs was transplanted though tail vein injection (1\u202f\u00d7\u202f10\n                      <jats:sup>6<\/jats:sup>\n                      , 0.5\u202fmL). The myelin basic protein (MBP), amyloid precursor protein (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -APP), nitric oxide (NO), glutathione (GSH) and interleukin (IL-1\u03b2) were determined at 1, 2, 4 and 8\u202fweeks after transplantation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The CP value of TX mice increased at 4 (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.029) and 8\u202fweeks (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.037) after transplantation. FA values (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.026, 0.020, 0.037) and the volume of neural fibers (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.016, 0.023, 0.018) increased at 2, 4 and 8\u202fweeks after transplantation. The pathological indexes of demyelination (MBP) and axon injury (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -APP) improved after BMSCs transplantation. The brain copper content decreased at 4 and 8\u202fweeks after transplantation (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.024, 0.038). The indexes of oxidative stress (NO and GSH) and inflammation (IL-1\u03b2) of TX mice were improved after transplantation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BMSCs can ameliorate WD extrapyramidal neural network injury. The mechanism may be related to reducing copper deposition and alleviating oxidative stress and inflammatory response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fncel.2025.1648155","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T06:27:55Z","timestamp":1765780075000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Study on the effect of mesenchymal stem cells on neural injury, inflammation and copper content in Wilson disease"],"prefix":"10.3389","volume":"19","author":[{"given":"Xiang-xue","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao-ling","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingbang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1097\/WCO.0000000000000837","article-title":"Wilson disease","volume":"33","author":"Aggarwal","year":"2020","journal-title":"Curr. Opin. Neurol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1007\/s00259-021-05439-4","article-title":"Firefly luciferase offers superior performance to AkaLuc for tracking the fate of administered cell therapies","volume":"49","author":"Amadeo","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fneur.2020.00005","article-title":"Recognition of brain metastases using gadolinium-enhanced SWI MRI: proof-of-concept study","volume":"11","author":"Ceballos-Ceballos","year":"2020","journal-title":"Front. Neurol."},{"key":"ref4","first-page":"703","article-title":"Effect of bone marrow stem cell transplantation on cerebral and renal copper metabolism in early stage mice with hepatolenticular degeneration","volume":"34","author":"Chen","year":"2013","journal-title":"J. Sun Yat-sen Univ."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/s41392-022-01229-y","article-title":"Copper homeostasis and cuproptosis in health and disease","volume":"7","author":"Chen","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"101911","DOI":"10.1016\/j.arr.2023.101911","article-title":"Abnormal white matter changes in Alzheimer's disease based on diffusion tensor imaging: A systematic review","volume":"87","author":"Chen","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1159\/000534767","article-title":"Prediction of MCI progression to AD based on DTI-derived diffusion parameters: construction and validation of a nomogram","volume":"86","author":"Cheng","year":"2023","journal-title":"Eur. Neurol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/s41573-021-00233-1","article-title":"Targeting oxidative stress in disease: promise and limitations of antioxidant therapy","volume":"20","author":"Forman","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s10534-024-00640-y","article-title":"Effect of primary copper metabolism disturbance on elemental, protein, and lipid composition of the organs in Jackson toxic milk mouse","volume":"38","author":"Hadrian","year":"2025","journal-title":"Biometals"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.cld.2022.03.008","article-title":"Wilson disease in children","volume":"26","author":"Kerkar","year":"2022","journal-title":"Clin. Liver Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"11772719241297169","DOI":"10.1177\/11772719241297169","article-title":"Systematic analysis and insights into the mutation Spectrum and ethnic differences in ATP7B mutations associated with Wilson disease","volume":"19","author":"Lao","year":"2024","journal-title":"Biomark. Insights"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"100272","DOI":"10.1016\/j.prdoa.2024.100272","article-title":"Zinc gluconate for Wilson disease","volume":"11","author":"Le Doux","year":"2024","journal-title":"Clin. Park. Relat. Disord."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s12951-023-01828-z","article-title":"Comparative study of extracellular vesicles derived from mesenchymal stem cells and brain endothelial cells attenuating blood-brain barrier permeability via regulating Caveolin-1-dependent ZO-1 and Claudin-5 endocytosis in acute ischemic stroke","volume":"21","author":"Li","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e0243014","DOI":"10.1371\/journal.pone.0243014","article-title":"BMSCs differentiated into neurons, astrocytes and oligodendrocytes alleviated the inflammation and demyelination of EAE mice models","volume":"16","author":"Liu","year":"2021","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0300-483x(97)00133-9","article-title":"Regional brain distribution of metallothionein, zinc and copper in toxic milk mutant and transgenic mice","volume":"124","author":"Ono","year":"1997","journal-title":"Toxicology"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.omtm.2022.08.004","article-title":"Full-length ATP7B reconstituted through protein trans-splicing corrects Wilson disease in mice","volume":"26","author":"Padula","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e171281","DOI":"10.1172\/jci.insight.171281","article-title":"Genome editing without nucleases confers proliferative advantage to edited hepatocytes and corrects Wilson disease","volume":"8","author":"Padula","year":"2023","journal-title":"JCI Insight"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1002\/jcb.30323","article-title":"Copper regulation disturbance linked to oxidative stress and cell death during Zika virus infection in human astrocytes","volume":"123","author":"Puig-Pijuan","year":"2022","journal-title":"J. Cell. Biochem."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1055\/s-0043-1761926","article-title":"Pathological spectrum and \u03b2-APP immunoreactivity as a diagnostic tool of diffuse axonal injury following traumatic brain injury: a novel classification","volume":"15","author":"Sharma","year":"2023","journal-title":"J. Lab. Physicians."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cger.2019.08.002","article-title":"Parkinson disease epidemiology, pathology, genetics, and pathophysiology","volume":"36","author":"Simon","year":"2020","journal-title":"Clin. Geriatr. Med."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"183077","DOI":"10.1016\/j.bbamem.2019.183077","article-title":"Myelin basic protein (MBP) charge variants show different sphingomyelin-mediated interactions with myelin-like lipid monolayers","volume":"1862","author":"Widder","year":"2020","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"3749","DOI":"10.1007\/s10072-020-04973-7","article-title":"Study on different pathogenic factors in different disease stages of patients with Wilson disease","volume":"42","author":"Xiangxue","year":"2021","journal-title":"Neurol. Sci."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.reth.2024.03.005","article-title":"Research progress in stem cell therapy for Wilson disease","volume":"27","author":"Xiong","year":"2024","journal-title":"Regen. Ther."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"109286","DOI":"10.1016\/j.clim.2023.109286","article-title":"Myelin basic protein and index for neuro-Beh\u00e7et's disease","volume":"250","author":"Zhan","year":"2023","journal-title":"Clin. Immunol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e21010","DOI":"10.1016\/j.heliyon.2023.e21010","article-title":"BMSCs alleviate liver cirrhosis by regulating Fstl1\/Wnt\/\u03b2-catenin signaling pathway","volume":"9","author":"Zhangdi","year":"2023","journal-title":"Heliyon"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e132496","DOI":"10.5812\/ijpr-132496","article-title":"NBP cytoprotective effects promoting neuronal differentiation in BMSCs by inhibiting the p65\/Hes1 pathway","volume":"22","author":"Zhao","year":"2023","journal-title":"Iran. J. Pharm. Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e01459","DOI":"10.1002\/brb3.1459","article-title":"Injury factors and pathological features of toxic milk mice during different disease stages","volume":"9","author":"Zhou","year":"2019","journal-title":"Brain Behav."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.jns.2016.02.006","article-title":"Diffusion tensor imaging of the extracorticospinal network in the brains of patients with Wilson disease","volume":"362","author":"Zhou","year":"","journal-title":"J. Neurol. Sci."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"362","DOI":"10.4103\/0028-3886.141221","article-title":"Characterizing brain mineral deposition in patients with Wilson disease using susceptibility-weighted imaging","volume":"62","author":"Zhou","year":"2014","journal-title":"Neurol. India"},{"key":"ref30","first-page":"352","article-title":"Resting state functional magnetic resonance imaging of extrapyramidal brain nuclei in patients with hepatolenticular degeneration","volume":"49","author":"Zhou","year":"","journal-title":"Chin. J. Neurol."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2025.1648155\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T06:27:56Z","timestamp":1765780076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2025.1648155\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,15]]},"references-count":30,"alternative-id":["10.3389\/fncel.2025.1648155"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2025.1648155","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,15]]},"article-number":"1648155"}}