Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Koch, Henner UNSPECIFIED UNSPECIFIED UNSPECIFIED Niturad, Cristina E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Theiss, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Bien, Christian G. UNSPECIFIED orcid.org/0000-0003-2225-8654 UNSPECIFIED Elger, Christian UNSPECIFIED orcid.org/0000-0002-2531-6701 UNSPECIFIED Wandinger, Klaus-Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Vincent, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Malter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Kortvelyessy, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Lerche, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Dihne, Marcel UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language ANTIBODY; AUTOANTIBODIES; MECHANISMS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15111