Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown

Yu Zhang; Antony R Warden; Khan Zara Ahmad; Yanlei Liu; Xijun He; Minqiao Zheng; Xinlong Huo; Xiao Zhi; Yuqing Ke; Hongxia Li; Sijia Yan; Wenqiong Su; Deng Cai; Xianting Ding

doi:10.34133/2021/9873545

Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown

Research (Wash D C). 2021 Jul 8:2021:9873545. doi: 10.34133/2021/9873545. eCollection 2021.

Authors

Yu Zhang¹, Antony R Warden¹, Khan Zara Ahmad¹, Yanlei Liu², Xijun He³, Minqiao Zheng⁴, Xinlong Huo⁵, Xiao Zhi¹, Yuqing Ke¹, Hongxia Li¹, Sijia Yan¹, Wenqiong Su¹, Deng Cai⁶, Xianting Ding¹

Affiliations

¹ 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.
² 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.
³ Department of Neurosurgery, Wenling Hospital Affiliated to Wenzhou Medical University, Chuan'an Nan Road, Chengxi Subdistrict, Wenling, 317500 Zhejiang, China.
⁴ Central Laboratory, Wenling Hospital Affiliated to Wenzhou Medical University, Chuan'an Nan Road, Chengxi Subdistrict, Wenling, 317500 Zhejiang, China.
⁵ Department of Neurology, Wenling Hospital Affiliated to Wenzhou Medical University, Chuan'an Nan Road, Chengxi Subdistrict, Wenling, 317500 Zhejiang, China.
⁶ Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, China.

Abstract

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⁺/CD45^-/DAPI⁺ 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 (p < 0.05). Meanwhile, the number of CNCs is significantly higher in stroke patients than in negative subjects (p < 0.0001). 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.