Universität zu Köln

Pernhorst, Katharina, Herms, Stefan ORCID: 0000-0002-2786-8200, Hoffmann, Per ORCID: 0000-0002-6573-983X, Cichon, Sven ORCID: 0000-0002-9475-086X, Schulz, Herbert, Sander, Thomas, Schoch, Susanne, Becker, Albert J. and Grote, Alexander (2013). TLR4, ATF-3 and IL8 inflammation mediator expression correlates with seizure frequency in human epileptic brain tissue. Seizure, 22 (8). S. 675 - 679. LONDON: W B SAUNDERS CO LTD. ISSN 1532-2688

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Abstract

Purpose: Data from animal models has nicely shown that inflammatory processes in the central nervous system (CNS) can modulate seizure frequency. However, a potential relationship between the modulation of seizure frequency and gene expression of key inflammatory factors in human epileptic tissue is still unresolved. Brain tissue from pharmacoresistant patients with mesial temporal lobe epilepsy (mTLE) provides a unique prerequisite for clinico-neuropathological correlations. Here, we have concentrated on gene expression of the human key inflammatory mediators, TLR4, ATF-3 and IL8, in correlation to seizure frequency and additional clinical parameters in human epileptic brain tissue of pharmacoresistant mTLE patients. Furthermore, we characterized the cell types expressing the respective proteins in epileptic hippocampi. Methods: Total RNAs were isolated from n = 26 hippocampi of pharmacoresistant mTLE patients using AllPrep DNA/RNA Mini Kit. cRNA was used for hybridization on Human HT-12 v3 Expression BeadChips with Illumina Direct Hybridization Assay Kit and resulting gene expression data was normalized based on the Illumina BeadStudio software suite by means of quantile normalization with background subtraction. Corresponding human hippocampal sections for immunohistochemistry were probed with antibodies against TLR4, ATF-3, IL8 and glial fibrillary acidic protein (GFAP), neuronal nuclear protein (NeuN) and the microglial marker HLA-DR. Results: We observed abundant TLR4 gene expression to relate to seizure frequency per month. For ATF-3, we found an inverse correlation of expression to seizure frequency. Lower expression of IL8 was significantly associated with high seizure frequency. Further, we detected TLR4 expression in neurons and GFAP-positive astrocytes of pharmacoresistant mTLE patients. Only neurons of human epileptic hippocampi express ATF-3. IL8 was expressed in microglia and reactive astrocytes. Conclusion: Our results suggest a differential correlation of key inflammatory factor expression in epileptic hippocampi and seizure frequency in patients. The modulation of such processes may open new therapeutic perspectives for treating seizures. (C) 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pernhorst, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Herms, Stefan UNSPECIFIED orcid.org/0000-0002-2786-8200 UNSPECIFIED Hoffmann, Per UNSPECIFIED orcid.org/0000-0002-6573-983X UNSPECIFIED Cichon, Sven UNSPECIFIED orcid.org/0000-0002-9475-086X UNSPECIFIED Schulz, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Sander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoch, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Albert J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grote, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-475510
DOI:	10.1016/j.seizure.2013.04.023
Journal or Publication Title:	Seizure
Volume:	22
Number:	8
Page Range:	S. 675 - 679
Date:	2013
Publisher:	W B SAUNDERS CO LTD
Place of Publication:	LONDON
ISSN:	1532-2688
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TEMPORAL-LOBE EPILEPSY; ACTIVATING TRANSCRIPTION FACTOR-3; NEGATIVE REGULATOR; SURGERY; NEURONS; SYSTEM Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47551