PURPOSE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common drug-resistant epilepsy. Despite major advances in epilepsy research, the epileptogenesis of the MTLE-HS is not well understood. The altered neuroimmune response is one of the pathomechanisms linked to progressive epileptogenesis in MTLE-HS, and understanding its role may help design future cures for pharmaco-resistant MTLE-HS. Here, the neuroimmune function was evaluated by the assessment of cytokine-chemokine profiles in brain samples from the hippocampus of patients with MTLE-HS. METHODS: Brain samples from patients with MTLE-HS collected during epileptosurgical resection (n = 21) were compared to those obtained from autopsy controls (n = 13). The typing of HS was performed according to ILAE consensus classification, and patients were additionally sorted into subgroups based on the severity of neuronal depletion (Wyler grading system). Differences between patients with MTLE-HS with and without a history of febrile seizures were also assessed. RNA was isolated from native samples, and real-time gene expression analysis of cytokine-chemokine profiles, i.e., levels of IL-1β, IL-6, IL-10, IL-18, CCL2, CCL3, CCL4, and STAT3, was carried out by qRT-PCR methodology. RESULTS: Upregulation of IL-1β (p = 0.001), IL-18 (p = 0.0018), CCL2 (p = 0,0377), CCL3 (p < 0.001), and CCL4 (p < 0.001) in MTLE-HS patients was detected when compared to the post-mortem hippocampal samples collected from autopsy controls. The STAT3 expression was higher in more severe neuronal loss and glial scaring determined by different Wyler grades in HS patients. Furthermore, cytokine-chemokine profiles were not different in MTLE-HS patients with or without febrile seizures. CONCLUSION: The upregulation of specific cytokines and chemokines in MTLE-HS provides evidence that the neuroinflammatory process contributes to MTLE epileptogenesis. History of febrile seizures did not alter the immune profiles. Specific immune mediators and related immune pathways represent potential therapeutic targets for seizure control and pharmacoresistancy prevention in MTLE associated with hippocampal sclerosis.

Brno Epilepsy Center Department of Neurology St Anne's University Hospital and Medical Faculty of Masaryk University Brno Czech Republic

Department of Neurosurgery St Anne´s University Hospital Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pathology St Anne´s University Hospital Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pediatric Neurology Brno Epilepsy Center University Hospital Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pediatric Neurology Brno Epilepsy Center University Hospital Faculty of Medicine Masaryk University Brno Czech Republic; Ondrej Slaby Research Group Central European Institute of Technology Brno Czech Republic

Department of Pediatric Neurology Brno Epilepsy Center University Hospital Faculty of Medicine Masaryk University Brno Czech Republic; Ondrej Slaby Research Group Central European Institute of Technology Brno Czech Republic; Division of Clinical Behavioral Neuroscience Department of Pediatrics University of Minnesota Minneapolis MN USA

Division of Clinical Behavioral Neuroscience Department of Pediatrics University of Minnesota Minneapolis MN USA; Center for Magnetic Resonance Research Department of Radiology University of Minnesota Minneapolis MN USA

Ondrej Slaby Research Group Central European Institute of Technology Brno Czech Republic

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