Koch, Henner, Niturad, Cristina E., Theiss, Stephan, Bien, Christian G. ORCID: 0000-0003-2225-8654, Elger, Christian ORCID: 0000-0002-2531-6701, Wandinger, Klaus-Peter, Vincent, Angela, Malter, Michael, Kortvelyessy, Peter, Lerche, Holger and Dihne, Marcel (2019). In vitro neuronal network activity as a new functional diagnostic system to detect effects of Cerebrospinal fluid from autoimmune encephalitis patients. Sci Rep, 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

The intent of this study was to investigate if cerebrospinal fluid (CSF) from autoimmune encephalitis (AE) patients regulates in vitro neuronal network activity differentially to healthy human control CSF (hCSF). To this end, electrophysiological effects of CSF from AE patients or hCSF were measured by in vitro neuronal network activity (ivNNA) recorded with microelectrode arrays (MEA). CSF from patients with either N-methyl-D-aspartate-receptor-antibody (pCSF(NMDAR), n = 7) or Leucine-rich-glioma-inactivated-1-Ab (pCSF(LGI1), n = 6) associated AE suppressed global spiking activity of neuronal networks by a factor of 2.17 (p < 0.05) or 2.42 (p < 0.05) compared to hCSF. The former also suppressed synchronous network bursting by a factor of 1.93 (p < 0.05) in comparison to hCSF (n = 13). As a functional diagnostic test, this parameter reached a sensitivity of 86% for NMDAR-Ab- and 100% for LGI1-Ab-associated AE vs. hCSF at a specificity of 85%. To explore if modulation at the NMDAR influences effects of hCSF or pathological CSF, we applied the NMDAR-antagonist 2-Amino-5-phosphono-pentanoic acid (AP5). In CSF from NMDAR-Ab-associated AE patients, spike rate reduction by AP5 was more than 2-fold larger than in hCSF (p < 0.05), and network burst rate reduction more than 18-fold (p < 0.01). Recording ivNNA might help discriminating between functional effects of CSF from AE patients and hCSF, and thus could be used as a functional diagnostic test in AE. The pronounced suppression of ivNNA by CSF from NMDAR-Ab-associated AE patients and simultaneous antagonism at the NMDAR by AP5, particularly in burst activity, compared to hCSF plus AP5, confirms that the former contains additional ivNNA-suppressing factors.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koch, HennerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niturad, Cristina E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Theiss, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bien, Christian G.UNSPECIFIEDorcid.org/0000-0003-2225-8654UNSPECIFIED
Elger, ChristianUNSPECIFIEDorcid.org/0000-0002-2531-6701UNSPECIFIED
Wandinger, Klaus-PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vincent, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malter, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kortvelyessy, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lerche, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dihne, MarcelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-151111
DOI: 10.1038/s41598-019-41849-z
Journal or Publication Title: Sci Rep
Volume: 9
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ANTIBODY; AUTOANTIBODIES; MECHANISMSMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15111

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