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

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-1ß, 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-1ß and IL-10. IL-10 release was maximal on day 1, IL-1ß release peaked at day 8. No correlation between local hippocampal IL-1ß concentrations and IL-1ß blood levels was found. CONCLUSION: The release kinetics of IL-1ß 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.

Is there a role for microRNAs in epilepsy diagnostics?

INTRODUCTION: Epilepsy is a disease group that encompasses numerous brain pathologies, all leading to spontaneous seizures. Several diagnostic needs in the area of epilepsy diagnostics remain unmet. MicroRNAs (miRNAs) have emerged as potential biomarkers of disease. AREAS COVERED: We review clinical trials in epilepsy patients that investigated circulating miRNAs (CmiRNAs) as diagnostic biomarkers. EXPERT OPINION: The surveyed trial results are highly discordant and do not confidently support the identification of definite diagnostic biomarkers yet. Important progress comes from studies that identified measures to increase the discriminatory power of CmiRNAs, such as an investigation of specific miRNA compartments (e.g. exosomal vs. Argonaute-bound) or a study that developed point-of-care detection devices for CmiRNAs. No sufficient data elucidating the validity of CmiRNAs as biomarkers for monitoring disease status, the responses to treatment, the likelihood of treatment effects, prognosis, or safety or susceptibility are available. Further studies should adopt standardized designs and in-depth phenotyping to improve their validity. One of the most important and promising future research topics will be the identification of biomarkers for epileptogenesis in humans.