Summary Purpose:  Increasing evidence indicates that neuroinflammation plays a critical role in the pathogenesis of mesial temporal lobe epilepsy (MTLE). The aim of this study was to investigate the dynamic expression of interleukin (IL)–1β as a proinflammatory cytokine and microRNA (miR)‐146a as a posttranscriptional inflammation‐associated microRNA (miRNA) in the hippocampi of an immature rat model and children with MTLE. Methods:  To study the expression of IL‐1β and miR‐146a, we performed a reverse transcription polymerase chain reaction, Western blot, and real‐time quantitative PCR on the hippocampi of immature rats at 11 days of age. Expression was monitored in the acute, latent, and chronic stages of disease (2 h and 3 and 8 weeks after induction of lithium‐pilocarpine status epilepticus, respectively), and in control hippocampal tissues corresponding to the same timeframes. Similar expression methods were applied to hippocampi obtained from children with MTLE and normal controls. Key Findings:  The expression of IL‐1β and miR‐146a in both children and immature rats with MTLE differs according to the stage of MTLE development. Both IL‐1β and miR‐146a are significantly up‐regulated, but in opposite ways: IL‐1β expression is highest in the acute stage, when expression of miR‐146a is at its lowest level; miR‐146a expression is highest in the latent stage, when IL‐1β expression is at its lowest level. Both IL‐1β and miR‐146a are up‐regulated in the chronic stage, but not as much as in the other stages. Significance:  Our study is the first to focus on the expression of miR‐146a in the immature rat model of lithium‐pilocarpine MTLE and in children with MTLE. We have detected that the expression of proinflammatory cytokine IL‐1β and posttranscriptional inflammation‐associated miR‐146a is variable depending on the disease stage. Furthermore, both IL‐1β and miR‐146a are up‐regulated in immature rats and children with MTLE. Our findings elucidate the role of inflammation in the pathogenesis of MTLE in the immature rat model and children. Therefore, modulation of the IL‐1β–miR‐146a axis may be a novel therapeutic target in the treatment of MTLE.

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Background: Febrile infection-related epilepsy syndrome is associated with high mortality and morbidity rates. No systematic review of demographics, aetiologies, good treatment options, and causes of deaths has been performed. Thus, we aimed to focus on these factors to provide a structure for patient management and research. Methods: A deep literature search was performed in PubMed and Embase of all years until May 2019. Results: We retrieved 45 aSrticles: 3 multicentre cohort studies, 13 single-centre cohorts, 1 case series, and 28 case reports. We identified 229 cases: most were from Asia; 53% were males; 11.4% had several types of antibodies, and the most common was anti-glutamate receptor epsilon 2; 30% (69 cases) had good treatment outcomes; 12.2% died; and 56% remained with drug-resistant epilepsies. Univariate analysis revealed a statistically significant association between positive outcomes in Japan and China, the use of the ketogenic diet either acutely or chronically, and the use of steroids acutely or chronically. Taiwan showed a statistically significant association with negative outcomes. Multivariate logistic regression revealed the utilisation of the ketogenic diet in the acute phases (P = 0.008, OR = 3.613) and being in Japan (P = 0.003, OR = 3.146) as independent determinants of positive outcomes. Most of the deaths occurred because of the progress of the disease rather than complications of the drugs. Conclusions: Asians are more affected and several cases have antibodies. Positive outcomes are associated with being in Japan and the utilisation of the ketogenic diet in the acute phase.

BackgroundTumor necrosis factor-α (TNF-α), a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC) isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC) barrier dysfunction.MethodsBend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL). RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER). p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability.ResultsWe observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA) transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER.ConclusionsTaken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF-α signaling to RhoA, and that this plays a critical role in signaling F-actin rearrangement and barrier dysfunction in BMECs.

Background and purpose: The clinical and radiological features of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) diseases vary among the patients and studies. In addition, the clinical significance of MOG-Ab for the diagnosis, treatment, and prognosis is not yet established. Therefore, we aimed to evaluate the clinical, radiological, treatments and outcome features of MOG-Ab diseases in Central Southern part of China. Methods: A retrospective study of children with MOG-Ab disease was carried out from January 2015 to October 2018. Demographics, clinical features, treatments, and outcomes were reviewed. Some of the clinical information was compared including the annualized relapse rates (ARRs) before and after treatment with disease-modifying drugs (DMDs). Results: Twenty-five patients with MOG-Ab disease were recruited. The onset age ranged from 3 to 12.4 years old. 13 were females and 12 were males. The median follow-up period was 15 months (range 7–63). Most of the cases that aged ≤9 years presented with fever (47.4%), encephalopathy (47.4%), and lesions on white matter and/or deep gray matter (52.6%). While most of those aged above 9 years presented with optic neuritis (ON) (66.7%), and lesions on spinal cord and/or optic nerve (50%). Until the last follow-up, 10 (40%) cases had multiphasic courses while 15 (60%) had a monophasic course, and the mean follow-up time was statistically significant (10.67 vs. 31 months, p = 0.0001). DMDs such as rituximab (RTX) or/and azathioprine (AZP) or mycophenolate mofetil (MMF) were used at least once in 56% of the cases. The ARR before and after treatment was 2.4 and 0 respectively ( p < 0.05). The median Expanded Disability Status Scale scores of our study were 0 (range 0–2). 96% (24/25) of the cases had a full recovery. Conclusions: MOG-Ab disease among Chinese children share the same clinical characteristics with Caucasians. However, the Chinese children seem to have a better prognosis than Caucasians. There is an age-dependent phenotypes, as brain involvement is more frequently seen in children younger or equal to 9 years while ON and neuromyelitis optica spectrum disorders are commonly seen in children older than 9 years. DMDs, such as AZA, MMF or RTX, can reduce the ARR.

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The role of Toll-like receptor 4 (TLR4) in the activation of innate immunity has been extensively studied in the past several years. Here, we are the first to report that myeloid-related protein 8 (MRP8), an endogenous TLR4 ligand, is involved in the epileptogenesis of mesial temporal lobe epilepsy (MTLE). We find that the expression of MRP8, TLR4, and interleukin 1-β (IL-1β) was upregulated in a MTLE model during both acute and chronic disease stages. We next investigated the possible roles played by astrocytes, which have been shown to be the major source of IL-1β during epilepsy. Stimulation via MRP8 led to the induction of IL-1β in astrocytes in vitro, accompanied by the activation of Nuclear Factor-κB, while knockdown of TLR4 or inhibition of NF-κB in astrocytes prevented this IL-1β induction. Thus, MRP8 may potentiate the perpetuation of MTLE by activating the NF-κB pathway in astrocytes, and could be a new target for anticonvulsant therapies.