Flow Cytometry Characterization of Cerebrospinal Fluid Monocytes in Patients With Postoperative Cognitive Dysfunction: A Pilot Study

Miles Berger, David M Murdoch, Janet S Staats, Cliburn Chan, Jake P Thomas, Grant E Garrigues, Jeffrey N Browndyke, Mary Cooter, Quintin J Quinones, Joseph P Mathew, Kent J Weinhold, MADCO-PC Study Team, Cindy L Amundsen, Shahrukh Bengali, Brian E Brigman, W Michael Bullock, Jessica Carter, Joseph Chapman, Vanessa Cheong Yee Ching, Harvey J Cohen, Brian Colin, Thomas A D’Amico, Michael J Devinney, James K DeOrio, Tressa Ellet, Ramon M Esclamado, Michael N Ferrandino, Jeffrey Gadsden, Grant E Garrigues, Jason Guercio, Ashraf Habib, David H Harpole, Mathew G Hartwig, Ehimemen Iboaya, Brant A Inman, Anver Khan, Sandhya Lagoo-Deenadayalan, Paula S Lee, Walter T Lee, John Lemm, Howard Levinson, Christopher Mantyh, David L McDonagh, John Migaly, Suhail K Mithani, Eugene Moretti, Judd W Moul, Mark F Newman, Katherine Ni, Brian Ohlendorf, Alexander Perez, Andrew C Peterson, Vikram Ponussamy, Glenn M Preminger, Cary N Robertson, Sanziana A Roman, Scott Runyon, Aaron Sandler, Randall P Scheri, S Kendall Smith, Leonard Talbot, Julie K M Thacker, Betty C Tong, Alexander Tu, Steven N Vaslef, Nathan Waldron, Xueyuan Wang, Heather Whitson, Victoria Wickenheisser, Christopher Young, Miles Berger, David M Murdoch, Janet S Staats, Cliburn Chan, Jake P Thomas, Grant E Garrigues, Jeffrey N Browndyke, Mary Cooter, Quintin J Quinones, Joseph P Mathew, Kent J Weinhold, MADCO-PC Study Team, Cindy L Amundsen, Shahrukh Bengali, Brian E Brigman, W Michael Bullock, Jessica Carter, Joseph Chapman, Vanessa Cheong Yee Ching, Harvey J Cohen, Brian Colin, Thomas A D’Amico, Michael J Devinney, James K DeOrio, Tressa Ellet, Ramon M Esclamado, Michael N Ferrandino, Jeffrey Gadsden, Grant E Garrigues, Jason Guercio, Ashraf Habib, David H Harpole, Mathew G Hartwig, Ehimemen Iboaya, Brant A Inman, Anver Khan, Sandhya Lagoo-Deenadayalan, Paula S Lee, Walter T Lee, John Lemm, Howard Levinson, Christopher Mantyh, David L McDonagh, John Migaly, Suhail K Mithani, Eugene Moretti, Judd W Moul, Mark F Newman, Katherine Ni, Brian Ohlendorf, Alexander Perez, Andrew C Peterson, Vikram Ponussamy, Glenn M Preminger, Cary N Robertson, Sanziana A Roman, Scott Runyon, Aaron Sandler, Randall P Scheri, S Kendall Smith, Leonard Talbot, Julie K M Thacker, Betty C Tong, Alexander Tu, Steven N Vaslef, Nathan Waldron, Xueyuan Wang, Heather Whitson, Victoria Wickenheisser, Christopher Young

Abstract

Animal models suggest postoperative cognitive dysfunction may be caused by brain monocyte influx. To study this in humans, we developed a flow cytometry panel to profile cerebrospinal fluid (CSF) samples collected before and after major noncardiac surgery in 5 patients ≥60 years of age who developed postoperative cognitive dysfunction and 5 matched controls who did not. We detected 12,654 ± 4895 cells/10 mL of CSF sample (mean ± SD). Patients who developed postoperative cognitive dysfunction showed an increased CSF monocyte/lymphocyte ratio and monocyte chemoattractant protein 1 receptor downregulation on CSF monocytes 24 hours after surgery. These pilot data demonstrate that CSF flow cytometry can be used to study mechanisms of postoperative neurocognitive dysfunction.

Trial registration: ClinicalTrials.gov NCT03273335.

Conflict of interest statement

Conflicts of interest: MB acknowledges research funding from Minnetronix, Inc, for a study unrelated to the topic of this manuscript, material support from Massimo for another study unrelated to the topic of this manuscript, and private consulting income for a legal case related to postoperative cognition in an older adult. The rest of the authors have no other conflicts to report.

Figures

Figure 1.
Figure 1.
CSF Flow Cytometry and POCD. A) Changes in Monocytes and Monocyte Surface Marker Expression in a Representative Patient with Postoperative Cognitive Dysfunction (POCD). A) Upper panel represents side scatter (SSC-A) versus forward scatter (FSC-A) plot used to identify monocytes (upper gate) versus lymphocytes (lower gate) and monocyte to lymphocyte ratio (Mono/Lymph). Lower panel represents CD14 versus CD16 staining on monocytes. B) Monocyte/lymphocyte ratio (Mono/Lymph) in the CSF of patients who did (vs did not) develop POCD at 6 weeks after surgery. C) MCP-1 receptor expression on CSF monocytes (i.e. CD192 fluorescence intensity) from patients who did (vs did not) develop POCD at 6 weeks after surgery. The middle line on each box plot represents the group median, while the upper and lower box edges show the inter-quartile range (IQR; 25th – 75th percentiles). The whiskers show the rest of the data, except when there are outliers, in which case the whiskers shows 1.5 times the IQR. The points past the whiskers are outliers (> 1.5 times the IQR).

Source: PubMed

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