The Interleukin 17 System in Cortical Lesions in Focal Cortical Dysplasias

Abstract

Focal cortical dysplasias (FCDs) are increasingly recognized as important causes of medically intractable epilepsy. To understand the potential role of the interleukin 17 (IL-17) system in the epileptogenesis of FCDs, we studied the expression patterns of the IL-17 system in 15 FCD type Ia (FCDIa), 12 FCD type IIa (FCDIIa), and 12 FCD type IIb (FCDIIb) cortical lesions and compared the results with those in cerebral cortex from 10 control patients. Protein levels of IL-17, IL-17 receptor (IL-17R), and downstream factors of the IL-17 pathway (nuclear factor-κB activator 1 [NFκB; ACT1] and NFκB-p65) were markedly elevated in FCDIa, FCDIIa, and FCDIIb. Moreover, protein levels of IL-17 and IL-17R positively correlated with the frequency of seizures in FCD patients. Immunostaining indicated that IL-17 and IL-17R are highly expressed in neuronal microcolumns, dysmorphic neurons, balloon cells, astrocytes, and vascular endothelial cells. Nuclear factor-κB activator 1 and NFκB-p65 were diffusely expressed in FCDs. In addition, we detected a few IL-17-positive, CD4-positive T lymphocytes in FCDIIa and FCDIIb but not in FCDIa. Taken together, these findings suggest that the overexpression of the IL-17 system and the activation of the IL-17 signal transduction pathway may be involved in the epileptogenicity of cortical lesions in FCDs, thus representing a novel potential target for antiepileptic therapy.

Evaluating an Etiologically Relevant Platform for Therapy Development for Temporal Lobe Epilepsy: Effects of Carbamazepine and Valproic Acid on Acute Seizures and Chronic Behavioral Comorbidities in the Theiler’s Murine Encephalomyelitis Virus Mouse Model

“…Human patients with viral infection-induced encephalitis who present with seizures during the acute infection period are up to 22 times more likely to develop spontaneous, unprovoked seizures than the general population (Annegers et al, 1988). More importantly, inflammation represents a significant risk factor for seizure induction and maintenance, with proinflammatory cytokines being highly expressed in various animal seizure models (Pernot et al, 2011;Vezzani and Friedman, 2011) and patients with epilepsy (Kan et al, 2012;He et al, 2013;Hu et al, 2014). In fact, some seizure-induced proinflammatory signaling molecules remain upregulated during epileptogenesis (VoutsinosPorche et al, 2004;Ravizza et al, 2008;Maroso et al, 2010) and may be essential to the establishment of spontaneous recurrent seizures associated with temporal lobe epilepsy (TLE) .…”

Comparison of electrocorticographic patterns with focal cortical dysplasia types in children with epilepsy

“…В зависимости от степени нарушения строения ко-ры, патологическая активность тканей может про-являться в большей или меньшей степени [2,9,25].…”

“…В некоторых публикациях высказывались предположения, что это связано с более выраженным нарушением нейрональной сети в области, содержащей баллонные клетки [27]. По другим данным, гигантские пирамидные нейроны, гигантские вставочные нейроны и бал-лонные клетки обладают выраженными признака-ми гипервозбудимости [2,25]. Ряд исследований до-казывает связь фокальных кортикальных дисплазий II типа со сложными изменениями медиаторных и рецепторных систем [28,29], что способствует син-хронизации и генерации приступов.…”

“…Также описано, что нейроны с извращенной ориентацией, с патологически сформированными дендритами не проявляют признаков гипервозбуди-мости, однако не отрицается наличие еще не из-ученных характеристик данных клеток, которые мо-гут приводить к гипервозбудимости [2,25].…”

Pyrrolidine Dithiocarbamate Alleviated Anxiety in Diabetic Mice

“…that NF-κB plays an important role in physiological and pathological functions in neurons of CNS [36,37] . It has been reported that NF-κB is involved in chronic neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease [38,39] .…”