{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:37:50Z","timestamp":1753893470460,"version":"3.41.2"},"reference-count":74,"publisher":"American Association for the Advancement of Science (AAAS)","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":188,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Sailing Program","award":["19YF1446900"],"award-info":[{"award-number":["19YF1446900"]}]},{"DOI":"10.13039\/501100004921","name":"Shanghai Jiao Tong University","doi-asserted-by":"crossref","award":["YG2021QN129","ZH2018QNA49","ZH2018QNA54","YG2016MS60","19X190020154"],"award-info":[{"award-number":["YG2021QN129","ZH2018QNA49","ZH2018QNA54","YG2016MS60","19X190020154"]}],"id":[{"id":"10.13039\/501100004921","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology commission of Shanghai Municipality","doi-asserted-by":"crossref","award":["2017SHZDZX01"],"award-info":[{"award-number":["2017SHZDZX01"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82073380","81701353","81871448"],"award-info":[{"award-number":["82073380","81701353","81871448"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Research"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n            Central nervous system diseases commonly occur with the destruction of the blood-brain barrier. As a primary cause of morbidity and mortality, stroke remains unpredictable and lacks cellular biomarkers that accurately quantify its occurrence and development. Here, we identify NeuN\n            <jats:sup>+<\/jats:sup>\n            \/CD45\n            <jats:sup>\u2212<\/jats:sup>\n            \/DAPI\n            <jats:sup>+<\/jats:sup>\n            phenotype nonblood cells in the peripheral blood of mice subjected to middle cerebral artery occlusion (MCAO) and stroke patients. Since NeuN is a specific marker of neural cells, we term these newly identified cells as circulating neural cells (CNCs). We find that the enumeration of CNCs in the blood is significantly associated with the severity of brain damage in MCAO mice (\n            <jats:inline-formula>\n              <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                <mml:mi>p<\/mml:mi>\n                <mml:mo>&lt;<\/mml:mo>\n                <mml:mn>0.05<\/mml:mn>\n              <\/mml:math>\n            <\/jats:inline-formula>\n            ). Meanwhile, the number of CNCs is significantly higher in stroke patients than in negative subjects (\n            <jats:inline-formula>\n              <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                <mml:mi>p<\/mml:mi>\n                <mml:mo>&lt;<\/mml:mo>\n                <mml:mn>0.0001<\/mml:mn>\n              <\/mml:math>\n            <\/jats:inline-formula>\n            ). These findings suggest that the amount of CNCs in circulation may serve as a clinical indicator for the real-time prognosis and progression monitor of the occurrence and development of ischemic stroke and other nervous system disease.\n          <\/jats:p>","DOI":"10.34133\/2021\/9873545","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T23:45:06Z","timestamp":1625787906000},"source":"Crossref","is-referenced-by-count":5,"title":["Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown"],"prefix":"10.34133","volume":"2021","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3065-588X","authenticated-orcid":false,"given":"Antony R.","family":"Warden","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khan Zara","family":"Ahmad","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanlei","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xijun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Wenling Hospital Affiliated to Wenzhou Medical University, Chuan\u2019an Nan Road, Chengxi Subdistrict, Wenling, 317500 ZhejiangChina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minqiao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Central Laboratory, Wenling Hospital Affiliated to Wenzhou Medical University, Chuan\u2019an Nan Road, Chengxi Subdistrict, Wenling, 317500 ZhejiangChina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinlong","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wenling Hospital Affiliated to Wenzhou Medical University, Chuan\u2019an Nan Road, Chengxi Subdistrict, Wenling, 317500 Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Zhi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Ke","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxia","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijia","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqiong","family":"Su","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deng","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1549-3499","authenticated-orcid":false,"given":"Xianting","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"issue":"6","key":"e_1_3_5_1_2","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/WCO.0000000000000248","article-title":"Blood-brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury","volume":"28","author":"Prakash R.","year":"2015","unstructured":"R. Prakash, and S. T. Carmichael, \u201cBlood-brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury,\u201d Current Opinion in Neurology, vol. 28, no. 6, pp. 556\u2013564, 2015","journal-title":"Current Opinion in Neurology"},{"issue":"46","key":"e_1_3_5_2_2","article-title":"NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage","volume":"114","author":"Casas A. I.","year":"2017","unstructured":"A. I. Casas, E. Geuss, P. W. M. Kleikers, S. Mencl, A. M. Herrmann, I. Buendia, J. Egea, S. G. Meuth, M. G. Lopez, C. Kleinschnitz, and H. H. H. W. Schmidt, \u201cNOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage,\u201d Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 46, article 12315, \u201312320, 2017","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"e_1_3_5_3_2","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-26636-6","article-title":"Metastatic brain tumors disrupt the blood-brain barrier and alter lipid metabolism by inhibiting expression of the endothelial cell fatty acid transporter Mfsd2a","volume":"8","author":"Tiwary S.","year":"2018","unstructured":"S. Tiwary, J. E. Morales, S. C. Kwiatkowski, F. F. Lang, G. Rao, and J. H. McCarty, \u201cMetastatic brain tumors disrupt the blood-brain barrier and alter lipid metabolism by inhibiting expression of the endothelial cell fatty acid transporter Mfsd2a,\u201d Scientific Reports, vol. 8, no. 1, article 8267, 2018","journal-title":"Scientific Reports"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2015.02.002"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.188"},{"issue":"2","key":"e_1_3_5_6_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation D. A.","year":"2019","unstructured":"D. A. Nation, M. D. Sweeney, A. Montagne, A. P. Sagare, L. M. D\u2019Orazio, M. Pachicano, F. Sepehrband, A. R. Nelson, D. P. Buennagel, M. G. Harrington, T. L. S. Benzinger, A. M. Fagan, J. M. Ringman, L. S. Schneider, J. C. Morris, H. C. Chui, M. Law, A. W. 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