Inflammation in pediatric epilepsies: Update on clinical features and treatment options

Granata, Tiziana; Fusco, Lucia; Matricardi, Sara; Tozzo, Alessandra; Janigro, Damir; Nabbout, Rima

doi:10.1016/j.yebeh.2021.107959

Cited by 7 publications

(10 citation statements)

References 112 publications

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“…On the opposite, inflammation can reduce KCC2 transcription altering NKCC/KCC2 ratio, chloride homeostasis, and GABA control of membrane excitability (Pozzi et al, 2020 ) as previously described also in tissues from adult DS patients (Ruffolo et al, 2018 ). Finally activated glia may release different pro-inflammatory cytokines such as interleukin 1β (IL1-β) or tumor necrosis factor α (TNFα), danger signals like high mobility group box 1 (HMBG1), chemokines like CCL2–4, the transforming growth factor-β (TGFβ), the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), prostaglandins, reactive oxygen, or nitrogen species (ROS and RNS, respectively) and complement factors that, through several transcriptional and post-translational effects, ultimately induce alterations of the blood-brain barrier permeability, neuronal hyperexcitability and seizures (Rana and Musto, 2018 ; Vezzani et al, 2019 ; Verhoog et al, 2020 ; Granata et al, 2022 ). Whether and how these mechanisms take part in DS development needs further investigation, especially considering that febrile seizures, that characterize DS, involve many of the above-mentioned molecules and mechanisms.…”

Section: Discussionmentioning

confidence: 99%

GABA tonic currents and glial cells are altered during epileptogenesis in a mouse model of Dravet syndrome

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Chiavegato

Gómez-Gonzalo

et al. 2022

Front. Cell. Neurosci.

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Dravet Syndrome (DS) is a rare autosomic encephalopathy with epilepsy linked to Nav1.1 channel mutations and defective GABAergic signaling. Effective therapies for this syndrome are lacking, urging a better comprehension of the mechanisms involved. In a recognized mouse model of DS, we studied GABA tonic current, a form of inhibition largely neglected in DS, in brain slices from developing mice before spontaneous seizures are reported. In neurons from the temporal cortex (TeCx) and CA1 region, GABA tonic current was reduced in DS mice compared to controls, while in the entorhinal cortex (ECx) it was not affected. In this region however allopregnanonole potentiation of GABA tonic current was reduced in DS mice, suggesting altered extrasynaptic GABAA subunits. Using THIP as a selective agonist, we found reduced δ subunit mediated tonic currents in ECx of DS mice. Unexpectedly in the dentate gyrus (DG), a region with high δ subunit expression, THIP-evoked currents in DS mice were larger than in controls. An immunofluorescence study confirmed that δ subunit expression was reduced in ECx and increased in DG of DS mice. Finally, considering the importance of neuroinflammation in epilepsy and neurodevelopmental disorders, we evaluated classical markers of glia activation. Our results show that DS mice have increased Iba1 reactivity and GFAP expression in both ECx and DG, compared to controls. Altogether we report that before spontaneous seizures, DS mice develop significant alterations of GABA tonic currents and glial cell activation. Understanding all the mechanisms involved in these alterations during disease maturation and progression may unveil new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

GABA tonic currents and glial cells are altered during epileptogenesis in a mouse model of Dravet syndrome

Goisis

Chiavegato

Gómez-Gonzalo

et al. 2022

Front. Cell. Neurosci.

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“…Neuroinflammation and BBB dysfunction may play an important role as potential mechanisms in promoting and sustaining epileptic activity ( 34 – 36 ). An enhanced BBB permeability is present in experimental models and clinical conditions.…”

Section: Pathogenesismentioning

confidence: 99%

“…The subsequent risk of developing chronic epilepsy is relatively low (10–15%) and may vary depending on the target antigen and prompt immunotherapy. Chronic epilepsy after antibody-mediated encephalopathies is usually characterized by drug-resistant seizures that may result from an ongoing inflammatory process that persists beyond the acute phase or as sequelae due to irreversible changes altering the neuronal networks and persisting after the inflammatory process resolves ( 34 , 39 ).…”

Section: Pathogenesismentioning

confidence: 99%

The Pharmacoresistant Epilepsy: An Overview on Existent and New Emerging Therapies

et al. 2021

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Epilepsy is one of the most common neurological chronic disorders, with an estimated prevalence of 0. 5 – 1%. Currently, treatment options for epilepsy are predominantly based on the administration of symptomatic therapy. Most patients are able to achieve seizure freedom by the first two appropriate drug trials. Thus, patients who cannot reach a satisfactory response after that are defined as pharmacoresistant. However, despite the availability of more than 20 antiseizure medications (ASMs), about one-third of epilepsies remain drug-resistant. The heterogeneity of seizures and epilepsies, the coexistence of comorbidities, and the broad spectrum of efficacy, safety, and tolerability related to the ASMs, make the management of these patients actually challenging. In this review, we analyze the most relevant clinical and pathogenetic issues related to drug-resistant epilepsy, and then we discuss the current evidence about the use of available ASMs and the alternative non-pharmacological approaches.

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“…In some cases, tissue destruction can occur which can lead to irreversible degradation of the nervous tissue with the appearance of various forms of clinically manifest dysfunctions (i.e., epilepsy, Alzheimer’s disease, Parkinson’s disease, systemic lupus erythematosus, etc.) [ 1 , 80 – 83 ].…”

Section: Biomarkers Involved In Inflammatory Diseasesmentioning

confidence: 99%

Point-of-care electrochemical testing of biomarkers involved in inflammatory and inflammatory-associated medical conditions

et al. 2022

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Recent years have shown that the diagnosis and monitoring of biomarkers involved in inflammatory-associated medical conditions such as cancer, neurological disorders, viral infections, or daily physical activities offer real benefits in increasing the quality of medical care and patient life quality. In this context, the use of integrated and portable platforms as point-of-care testing devices for biomedical analysis to enable early disease diagnosis and monitoring, which can be successfully used even at the patient’s bed, is an emergency nowadays. The development of low-cost, miniaturized, and portable, user-friendly devices that provide an answer in a timely manner, such as electrochemical sensors, is relevant for the elaboration of point-of-care testing devices. This review focuses on the recent progress in bioanalysis of both specific biomarkers and inflammatory-associated biomarkers present in several diseases like neoplasia, severe neurological disorders, viral infections, and usual physical activity and provides an overview of the state of the art over the most recent electrochemical (bio)sensors for the detection of inflammation-related biomarkers. Future perspectives of point-of-care testing to improve healthcare management are also discussed. Graphical abstract

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Inflammation in pediatric epilepsies: Update on clinical features and treatment options

Cited by 7 publications

References 112 publications

GABA tonic currents and glial cells are altered during epileptogenesis in a mouse model of Dravet syndrome

GABA tonic currents and glial cells are altered during epileptogenesis in a mouse model of Dravet syndrome

The Pharmacoresistant Epilepsy: An Overview on Existent and New Emerging Therapies

Point-of-care electrochemical testing of biomarkers involved in inflammatory and inflammatory-associated medical conditions

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