{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T23:52:17Z","timestamp":1778284337268,"version":"3.51.4"},"reference-count":28,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Lumbar spinal stenosis (LSS) is a common neurodegenerative condition. However, how neurogenic claudication develops with severe leg pain has not yet been clearly elucidated. Moreover, cerebrospinal fluid (CSF) physiology at the lumbosacral level is poorly understood because of the difficulties involved in quantification and visualization. Recent studies have suggested that assessment of mitochondrial function in CSF provides an indirect way to assess neurological disorders and an important feature of disease progression. In this study, we assessed the relevance of endogenous extracellular mitochondria in the CSF of rats after LSS. Mitochondrial changes within the CSF were analyzed following LSS at 1 week using flow cytometry. An increase in cell size and number was observed in CSF with LSS, and reactive oxygen species (ROS) levels were also increased within the CSF at 1 week in the LSS group. Elevated mitochondrial ROS and functional changes in the CSF are hallmarks of LSS. The present study is the first to demonstrate that elevated mitochondrial ROS within the CSF is a new index for the early detection of LSS. Moreover, it may represent a potential novel treatment target for LSS.<\/jats:p>","DOI":"10.3390\/diagnostics11050748","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:59:14Z","timestamp":1619099954000},"page":"748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Elevated Mitochondrial Reactive Oxygen Species within Cerebrospinal Fluid as New Index in the Early Detection of Lumbar Spinal Stenosis"],"prefix":"10.3390","volume":"11","author":[{"given":"Jin Young","family":"Hong","sequence":"first","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunseong","family":"Kim","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Jin","family":"Jeon","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junseon","family":"Lee","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5020-6723","authenticated-orcid":false,"given":"In-Hyuk","family":"Ha","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref_1","first-page":"1103","article-title":"Cerebrospinal fluid analysis","volume":"68","author":"Seehusen","year":"2003","journal-title":"Am. Fam. Physician"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Akiba, C., Bandai, H., Ito, Y., Maeda, T., Yamaguchi, K., Nakajima, M., and Miyajima, M. (2020). Cerebrospinal fluid leak presented with the C1-C2 sign caused by spinal canal stenosis: A case report. BMC Neurol., 20.","DOI":"10.1186\/s12883-020-01697-1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/jor.23448","article-title":"Cerebrospinal fluid dynamics at the lumbosacral level in patients with spinal stenosis: A pilot study","volume":"35","author":"Chun","year":"2017","journal-title":"J. Orthop. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.mehy.2018.06.008","article-title":"The possible impact of cervical stenosis on cephalad neuronal dysfunction","volume":"118","author":"Khachatryan","year":"2018","journal-title":"Med. Hypotheses"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1161\/STROKEAHA.117.017758","article-title":"Extracellular Mitochondria in Cerebrospinal Fluid and Neurological Recovery After Subarachnoid Hemorrhage","volume":"48","author":"Chou","year":"2017","journal-title":"Stroke"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1177\/1352458517699874","article-title":"Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment","volume":"24","author":"Leurs","year":"2018","journal-title":"Mult. Scler."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/ana.24515","article-title":"Reduced cerebrospinal fluid mitochondrial DNA is a biomarker for early-stage Parkinson\u2019s disease","volume":"78","author":"Pyle","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jns.2008.07.032","article-title":"Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression","volume":"275","author":"Regenold","year":"2008","journal-title":"J. Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nature18928","article-title":"Transfer of mitochondria from astrocytes to neurons after stroke","volume":"535","author":"Hayakawa","year":"2016","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nm.2736","article-title":"Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury","volume":"18","author":"Islam","year":"2012","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.mito.2016.12.003","article-title":"Increased levels of cell-free mitochondrial DNA in the cerebrospinal fluid of patients with multiple sclerosis","volume":"34","author":"Varhaug","year":"2017","journal-title":"Mitochondrion"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1097\/SHK.0000000000000160","article-title":"Cerebrospinal fluid mitochondrial DNA: A novel DAMP in pediatric traumatic brain injury","volume":"41","author":"Walko","year":"2014","journal-title":"Shock"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1159\/000237221","article-title":"8-OHdG in cerebrospinal fluid as a marker of oxidative stress in various neurodegenerative diseases","volume":"6","author":"Gmitterova","year":"2009","journal-title":"Neurodegener. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Podlesniy, P., Llorens, F., Puigros, M., Serra, N., Sepulveda-Falla, D., Schmidt, C., Hermann, P., Zerr, I., and Trullas, R. (2020). Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176298"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kim, H., Hong, J.Y., Lee, J., Jeon, W.J., and Ha, I.H. (2021). IL-1beta promotes disk degeneration and inflammation through direct injection of intervertebral disk in a rat lumbar disk herniation model. Spine J.","DOI":"10.1016\/j.spinee.2021.01.014"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jneumeth.2008.12.001","article-title":"A simple and rapid method to collect the cerebrospinal fluid of rats and its application for the assessment of drug penetration into the central nervous system","volume":"178","author":"Nirogi","year":"2009","journal-title":"J. Neurosci. Methods"},{"key":"ref_17","first-page":"5089046","article-title":"Comparison of DNA Extraction Protocols and Molecular Targets to Diagnose Tuberculous Meningitis","volume":"2017","author":"Palomo","year":"2017","journal-title":"Tuberc. Res. Treat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/157015909787602823","article-title":"Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options","volume":"7","author":"Uttara","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e5381","DOI":"10.7717\/peerj.5381","article-title":"Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis","volume":"6","author":"Dechsupa","year":"2018","journal-title":"PeerJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"24168","DOI":"10.18632\/aging.104105","article-title":"Oxidative stress mediates age-related hypertrophy of ligamentum flavum by inducing inflammation, fibrosis, and apoptosis through activating Akt and MAPK pathways","volume":"12","author":"Chuang","year":"2020","journal-title":"Aging"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2019). Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules, 24.","DOI":"10.3390\/molecules24081583"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2105607","DOI":"10.1155\/2019\/2105607","article-title":"Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View","volume":"2019","author":"Cenini","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113332","DOI":"10.1016\/j.expneurol.2020.113332","article-title":"Mitochondria focused neurotherapeutics for spinal cord injury","volume":"330","author":"Rabchevsky","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/ncpneuro0924","article-title":"Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis","volume":"4","author":"Henchcliffe","year":"2008","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Barcelos, I.P., Troxell, R.M., and Graves, J.S. (2019). Mitochondrial Dysfunction and Multiple Sclerosis. Biology, 8.","DOI":"10.3390\/biology8020037"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1093\/brain\/awz201","article-title":"A metabolic perspective on CSF-mediated neurodegeneration in multiple sclerosis","volume":"142","author":"Wentling","year":"2019","journal-title":"Brain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/978-1-4939-7778-9_7","article-title":"Biomarkers in Cerebrospinal Fluid: Analysis of Cell-Free Circulating Mitochondrial DNA by Digital PCR","volume":"1768","author":"Podlesniy","year":"2018","journal-title":"Methods Mol. Biol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/5\/748\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:51:16Z","timestamp":1760161876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/5\/748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,22]]},"references-count":28,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["diagnostics11050748"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11050748","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,22]]}}}