Role of Innate Immune Receptor TLR4 and its endogenous ligands in epileptogenesis

Paudel, Yam Nath; Angelopoulou, Efthalia; Akyüz, Enes; Piperi, Christina; Othman, Iekhsan; Shaikh, Mohd Farooq

doi:10.1016/j.phrs.2020.105172

Cited by 37 publications

(26 citation statements)

References 162 publications

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“…21 In addition, SARS-CoV-2 infection can induce a systemic in ammatory storm and release many pro-in ammatory factors, resulting in BBB destruction, damage of glia limitans, activation of Toll-like receptors in microglia, and astrocytes, and ultimately promoted neuroin ammation, which may severely disrupt brain homeostasis and cause neuronal death. 22,23 On the one hand, many studies have revealed that activating Toll-like receptors can cause epilepsy; 24,25 On the other hand, BBB disruption can cause entry of immune cells and serum proteins from peripheral blood into the brain, promoting the occurrence of epilepsy. 25,26 Finally, SARS-CoV-2 transcriptome had molecular similarities with the epitopes of human CNS protein, producing various autoantibodies and may eventually trigger autoimmunity to aggravate in ammatory storms.…”

Section: Discussionmentioning

confidence: 99%

Effect of COVID-19 Vaccination on Seizures in Patients With Epilepsy: a Multicenter, Retrospective Study

Fang

Qiao

Zhang

et al. 2021

Preprint

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Background: Previous study have shown that seizures may occur as a result of vaccination. This study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated with COVID-19 and to provide reference opinions for PWE to receive COVID-19 vaccine.Methods: We retrospectively enrolled PWE patients who were vaccinated against COVID-19 in the epilepsy centers of nine hospitals in China. The binary logistic regression analysis included variables with a P-value less than 0.1 in the univariate analysis.Results: The study included 290 patients, of which 40 (13.8%) developed seizures within 14 days after vaccination, whereas 250 (86.2%) remained seizure-free. The binary logistic regression analysis revealed statistical significance in seizures within three months before vaccination (P<0.001, OR=10.121, 95% CI: 4.301-23.816) and withdrawal or reduction of anti-seizures medications (ASM) during the peri-vaccination period (P=0.027, OR=4.452, 95% CI: 1.182-16.768). In addition, 32 of 33 patients (97.0%) who were seizure-free within three months before vaccination and had normal EEG results before vaccination did not have any seizures within 14 days following vaccination.Conclusions: SARS-CoV-2 may induce epilepsy through an inflammatory cascade. It is recommended to provide the COVID-19 vaccine to seizure-free patients for at least three months before vaccination, and the vaccination is safer if EEG result is normal. During peri-vaccination period, all PWE should be prohibited from reducing ASM dosage. PWE with well-controlled seizures who have discontinued ASM might consider resuming ASM during the peri-vaccination period if their EEG results are aberrant.

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Section: Discussionmentioning

confidence: 99%

Effect of COVID-19 Vaccination on Seizures in Patients With Epilepsy: a Multicenter, Retrospective Study

Fang

Qiao

Zhang

et al. 2021

Preprint

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“…TLR4 activates the TIR domain containing adaptor IFN-β (TrIF)-related adaptor molecule (TRAM). The TRAM combines with TRIF to induce late activation of MAPK and NF-κB ( 41 ) and ultimately to increase cytokine expression and inflammatory damage ( 42 , 43 ). NF-κB is a nuclear transcription factor closely related to immune regulation.…”

Section: Discussionmentioning

confidence: 99%

The Role of the Negative Regulation of Microglia-Mediated Neuroinflammation in Improving Emotional Behavior After Epileptic Seizures

Wang

Liu

et al. 2022

Front. Neurol.

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ObjectiveStudies have long shown that uncontrolled inflammatory responses in the brain play a key role in epilepsy pathogenesis. Microglias play an important role in epileptic-induced neuroinflammation, but their role after epileptic seizures is still poorly understood. Alleviating epilepsy and its comorbidities has become a key area of interest for pediatricians.MethodsA pilocarpine-induced rat model of epilepsy was established. The rats were randomly divided into four groups: a control group, epilepsy group, TLR4 inhibitor group (epilepsy+TAK-242), and NF-κB antagonist group (epilepsy+BAY11–7082).Results1. The results of TUNEL staining showed that the expression in rats in the epilepsy group was the most obvious and was significantly different from that in rats in the control, EP+BAY and EP+TAK groups. 2. The expression of TLR4 and NF-κB was highest in rats in the epilepsy group and was significantly different from that in rats in the control, EP+BAY and EP+TAK groups. 3. The fluorescence intensity and number of IBA-1-positive cells in rats in the epilepsy group were highest and significantly different from those in rats in the control, EP+BAY and EP+TAK groups. Western blot analysis of IBA-1 showed that the expression in rats in the epilepsy group was the highest and was statistically significant. 4. CD68 was the highest in rats in the epilepsy group and was statistically significant. 5. In the open-field experiment, the central region residence time of rats in the EP group was delayed, the central region movement distance traveled was prolonged, the total distance traveled was prolonged, and the average speed was increased. Compared with rats in the EP group, rats in the EP+BAY and EP+ TAK groups exhibited improvements to different degrees.ConclusionAt the tissue level, downregulation of the TLR4/NF-κB inflammatory pathway in epilepsy could inhibit microglial activation and the expression of the inflammatory factor CD68, could inhibit hyperphagocytosis, and inhibit the occurrence and exacerbation of epilepsy, thus improving cognitive and emotional disorders after epileptic seizures.

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“…LPS is the main component of their cell wall and, by engaging the TLR4 receptor, it can activate the MyD88-dependent signaling pathway in the lamina propria, resulting in the secretion of proinflammatory mediators that could trigger and perpetuate local inflammation ( Ghosh et al, 2020 ). Moreover, TLR4 signaling has been shown to promote neuroinflammation ( Paudel et al, 2020 ) and LPS administration in rodent models, both locally and systemically, results in seizure induction ( Hauss-Wegrzyniak et al, 2000 ; Maroso et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Is Gut Microbiota a Key Player in Epilepsy Onset? A Longitudinal Study in Drug-Naive Children

Ceccarani

Viganò

Ottaviano

et al. 2021

Front. Cell. Infect. Microbiol.

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Microbiota alterations have been recently investigated in individuals with epilepsy and in other neurological diseases as environmental factors that play a role, by acting through the gut-brain axis, in the pathological process. Most studies focus on the contribution of bacterial communities in refractory epilepsy and suggest a beneficial role of ketogenic diet in modulating the gut microbiota and seizure occurrence. However, they do not evaluate whether epilepsy itself alters the gut microbiota in these patients or if the gut microbial communities could contribute as a seizure trigger. In this pilot study, we performed 16S rRNA sequencing and investigated the gut microbial communities of eight children at their seizure onset and after anti-seizure was started (one year follow-up) and we compared microbial data with seven healthy children, age- and sex-matched. In drug-naive subjects, we observed a microbial signature that shared several features with those reported in refractory epilepsy, such as an increased abundance in Akkermansia spp. and Proteobacteria and a decreased relative abundance in Faecalibacterium spp.We suggest that a bacterial-mediated proinflammatory milieu could contribute to seizure occurrence in children with new onset of epilepsy, as already reported for individuals with drug-resistant epilepsy, and that it could vary during treatment in those who are drug-responsive.

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Role of Innate Immune Receptor TLR4 and its endogenous ligands in epileptogenesis

Cited by 37 publications

References 162 publications

Effect of COVID-19 Vaccination on Seizures in Patients With Epilepsy: a Multicenter, Retrospective Study

Effect of COVID-19 Vaccination on Seizures in Patients With Epilepsy: a Multicenter, Retrospective Study

The Role of the Negative Regulation of Microglia-Mediated Neuroinflammation in Improving Emotional Behavior After Epileptic Seizures

Is Gut Microbiota a Key Player in Epilepsy Onset? A Longitudinal Study in Drug-Naive Children

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