Autoantibodies against NMDAR subunit NR1 disappear from blood upon anesthesia

Johannes Teller; Carolin Jung; Justus B H Wilke; Svea-Dorothée Schimmelpfennig; Martin Hindermann; Lukas Hinken; Maria M Gabriel; Christine Fegbeutel; Andreas Schäfer; Hans Laser; Ralf Lichtinghagen; Hans Worthmann; Karin Weissenborn; Hannelore Ehrenreich

doi:10.1016/j.bbih.2022.100494

Autoantibodies against NMDAR subunit NR1 disappear from blood upon anesthesia

Brain Behav Immun Health. 2022 Aug 4:24:100494. doi: 10.1016/j.bbih.2022.100494. eCollection 2022 Oct.

Affiliations

¹ Department of Neurology, Hannover Medical School, Hannover, Germany.
² Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany.
³ Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
⁴ Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
⁵ Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
⁶ Center for Information Management, Hannover Medical School, Hannover, Germany.
⁷ Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany.

Abstract

Anesthetics penetrate the blood-brain-barrier (BBB) and - as confirmed preclinically - transiently disrupt it. An analogous consequence in humans has remained unproven. In mice, we previously reported that upon BBB dysfunction, the brain acts as 'immunoprecipitator' of autoantibodies against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB). We thus hypothesized that during human anesthesia, pre-existing NMDAR1-AB will specifically bind to brain. Screening of N = 270 subjects undergoing general anesthesia during cardiac surgery for serum NMDAR1-AB revealed N = 25 NMDAR1-AB seropositives. Only N = 14 remained positive post-surgery. No changes in albumin, thyroglobulin or CRP were associated with reduction of serum NMDAR1-AB. Thus, upon anesthesia, BBB opening likely occurs also in humans.

Keywords: BBB breakdown; Blood-brain-barrier opening; Cardiac surgery; Heart disease; Immunoglobulin class; Seroprevalence; Serum proteins.