Hippocampal Cytokine Release in Experimental Epileptogenesis—A Longitudinal In Vivo Microdialysis Study

Brain Sciences

Sven G. Meuth¹  Valentin Neubert²  Lara S. Costard²  Kai Siebenbrodt³  Felix Rosenow³  Sebastian Bauer³  Vanessa Schütz³  Kerstin Seidel⁴  Bernd Schmeck⁴  Daniel Alvarez-Fischer⁵ 

[1] Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany;Department of Neurology, Philipps University, 35037 Marburg, Germany;Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, University Hospital Frankfurt and LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, 60528 Frankfurt am Main, Germany;Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, 35037 Marburg, Germany;Institute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany;

关键词: epilepsy;    temporal lobe epilepsy;    inflammation;    hippocampal sclerosis;    rat model;   

DOI  :  10.3390/brainsci12050677

来源: DOAJ

【 摘 要 】

Background: Inflammation, particularly cytokine release, contributes to epileptogenesis by influencing the cerebral tissue remodeling and neuronal excitability that occurs after a precipitating epileptogenic insult. While several cytokines have been explored in this process, release kinetics are less well investigated. Determining the time course of cytokine release in the epileptogenic zone is necessary for precisely timed preventive or therapeutic anti-inflammatory interventions. Methods: Hippocampal extracellular levels of six cytokines and chemokines (IL-1β, IL-6, IL-10, CCL2, CCL3, and CCL5) were quantified at various time points during epileptogenesis in a rat model of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) using microdialysis (MD). Results: The analysis of microdialysates demonstrated consistent elevation at all time points during epileptogenesis for IL-1β and IL-10. IL-10 release was maximal on day 1, IL-1β release peaked at day 8. No correlation between local hippocampal IL-1β concentrations and IL-1β blood levels was found. Conclusion: The release kinetics of IL-1β are consistent with its established pro-epileptogenic properties, while the kinetics of IL-10 suggest a counter-regulatory effect. This proof-of-concept study demonstrates the feasibility of intraindividual longitudinal monitoring of hippocampal molecular inflammatory processes via repetitive MD over several weeks and sheds light on the kinetics of hippocampal cytokine release during epileptogenesis.

【 授权许可】

Unknown