mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment

Nature reviews. Neuroscience, Год журнала: 2024, Номер 25(5), С. 334 - 350

Опубликована: Март 26, 2024

Язык: Английский

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Neuroinflammation and Epilepsy: From Pathophysiology to Therapies Based on Repurposing Drugs

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4161 - 4161

Опубликована: Апрель 9, 2024

Neuroinflammation and epilepsy are different pathologies, but, in some cases, they so closely related that the activation of one pathologies leads to development other. In this work, we discuss three main cell types involved neuroinflammation, namely (i) reactive astrocytes, (ii) activated microglia, infiltration (iii) peripheral immune cells central nervous system. Then, how neuroinflammation interconnected describe use repurposing drugs with anti-inflammatory properties have been shown a beneficial effect models. This review reinforces idea compounds designed alleviate seizures need target not only caused by astrocytes microglia but also interaction these infiltrated cells.

Язык: Английский

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Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay

Frontiers in Pediatrics, Год журнала: 2023, Номер 11

Опубликована: Ноя. 21, 2023

Status epilepticus (SE) is a medical emergency resulting from the failure of mechanisms involved in seizure termination or initiation pathways abnormally prolonged seizures, potentially leading to long-term consequences, including neuronal death and impaired networks. It can eventually evolve refractory status (RSE), which administration benzodiazepine another anti-seizure medications (ASMs) had been ineffective, super-refractory (SRSE), persists for more than 24 h after general anesthesia. Objective present review highlight link between inflammation SE. Several preclinical clinical studies have shown that neuroinflammation contribute onset recurrence by increasing excitability. Notably, microglia astrocytes promote susceptibility. In fact, inflammatory mediators released glial cells might enhance excitation cause drug resistance recurrence. Understanding molecular could be crucial improving SE treatment, wich currently mainly addressed with benzodiazepines phenytoin, valproic acid, levetiracetam. IL-1β signal blockade Anakinra has promising results avoiding generalization epilepsy. Inhibiting converting enzyme (ICE)/caspase-1 also being investigated as possible target managing drug-resistant epilepsies. Targeting ATP-P2X7R signal, activates NLRP3 inflammasome triggers molecule release, avenue research. Interestingly, astaxanthin promise attenuating inhibiting signal. Furthermore, IL-6 using tocilizumab effective RSE reducing seizures patients febrile infection-related epilepsy syndrome (FIRES). Other potential approaches include ketogenic diet, may modulate pro-inflammatory cytokine production, use cannabidiol (CBD), demonstrated antiepileptic, neuroprotective, anti-inflammatory properties, targeting HMGB1-TLR4 axis. Clinical experience anti-cytokine agents such Tocilizumab limited, although promising. Nonetheless, Etanercept Rituximab efficacy only specific etiologies SE, autoimmune encephalitis. Overall, cytokines shows an innovative therapeutic option epilepsies providing chance directly addressing its underlying mechanisms, rather solely focusing on symptom control.

Язык: Английский

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The Contribution of Microglia and Brain-Infiltrating Macrophages to the Pathogenesis of Neuroinflammatory and Neurodegenerative Diseases during TMEV Infection of the Central Nervous System

Viruses, Год журнала: 2024, Номер 16(1), С. 119 - 119

Опубликована: Янв. 13, 2024

The infection of the central nervous system (CNS) with neurotropic viruses induces neuroinflammation and is associated development neuroinflammatory neurodegenerative diseases, including multiple sclerosis epilepsy. activation innate adaptive immune response, microglial, macrophages, T B cells, while required for efficient viral control within CNS, also neuropathology. Under healthy conditions, resident microglia play a pivotal role in maintaining CNS homeostasis. However, during pathological events, such as infection, become reactive, cells from periphery infiltrate into brain, disrupting homeostasis contributing to disease development. Theiler's murine encephalomyelitis virus (TMEV), picornavirus, used two distinct mouse models: TMEV-induced demyelination (TMEV-IDD) seizures, representing models epilepsy, respectively. These have contributed substantially our understanding pathophysiology MS seizures/epilepsy following serving critical tools identifying pharmacological targetable pathways modulate This review aims discuss host-pathogen interaction picornavirus shed light on current multifaceted roles played by macrophages context these complexes viral-induced disease.

Язык: Английский

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Cerebrospinal fluid and serum cytokine profiles in severe viral encephalitis with implications for refractory status epilepticus: a retrospective observational study

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 10, 2025

Background To identify new intervention targets, we explored the correlation between cytokines and development of refractory status epilepticus (RSE) in patients with severe viral encephalitis (SVE). Methods We examined characteristics 14 cerebrospinal fluid (CSF) serum, analyzing their acute symptomatic seizures prognosis. Furthermore, conducted a dynamic analysis differences correlations expression among SVE without seizures, those controlled RSE. Results included 161 SVE; incidence was 55.2%, mortality rate 5.5%. Notably, 18.9% these developed RSE, 20%. During early stage SVE, CSF interleukin (IL)-6 IL-8 levels were significantly higher, declining over time affecting IL-6 elevated RSE group compared to decreasing gradually independently serum cytokine levels. age independent risk factors for clinical utility. Conclusions Patients exhibit intrathecal storms, primarily characterized by IL-8, which influence The strong persistent hyperinflammation underscored is associated occurrence RSE; thus, are indicating potential anti-inflammatory targets.

Язык: Английский

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The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infection

Immunity, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Neuropathology of New-Onset Refractory Status Epilepticus (NORSE)

Journal of Neurology, Год журнала: 2023, Номер 270(8), С. 3688 - 3702

Опубликована: Апрель 20, 2023

Язык: Английский

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A Systematic Review of the Predictive and Diagnostic Uses of Neuroinflammation Biomarkers for Epileptogenesis

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6488 - 6488

Опубликована: Июнь 12, 2024

A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the of inflammatory mediators epileptogenesis, its association with seizure severity, and correlation drug-resistant epilepsy (DRE). The study analysed articles published JCR journals from 2019 to 2024. search strategy comprised MESH, free terms “Neuroinflammation”, selective searches following single biomarkers that had previously selected relevant literature: “High mobility group box 1/HMGB1”, “Toll-Like-Receptor 4/TLR-4”, “Interleukin-1/IL-1”, “Interleukin-6/IL-6”, “Transforming growth factor beta/TGF-β”, “Tumour necrosis factor-alpha/TNF-α”. These queries were all combined MESH “Epileptogenesis” “Epilepsy”. We found 243 related neuroinflammation, 356 biomarker type. After eliminating duplicates, 324 evaluated, 272 excluded 55 evaluated authors. total 21 included qualitative evaluation, including 18 case–control studies, 2 case series, 1 prospective study. As conclusion, this provides acceptable support five biomarkers, TNF-α some soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 IL-33. Certain receptors, cytokines, chemokines are examples neuroinflammation-related may be crucial early diagnosis refractory or connected control epileptic seizures. Their value will better defined future studies.

Язык: Английский

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Neuroimmune response and oxidative stress in the prefrontal cortex mediate seizure susceptibility in experimental colitis in male mice

Journal of Biochemical and Molecular Toxicology, Год журнала: 2024, Номер 38(7)

Опубликована: Июнь 26, 2024

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder. Oxidative stress and inflammatory responses have vital role in the pathophysiology of IBD as well seizure. associated with extraintestinal manifestations. This study aimed to explore relationship between colitis susceptibility seizures, focus on roles neuroinflammation oxidative acetic acid-induced mice. Forty male Naval Medical Research Institute mice were divided into four groups: control, colitis, pentylenetetrazole (PTZ), + PTZ. Colitis was induced by intrarectal administration acid, seizures intravenous injection PTZ 7 days postcolitis induction. Following measurement latency seizure, killed, their colons prefrontal cortex (PFC) dissected. Gene expression markers including interleukin-1β, tumor necrosis factor-alpha, NOD-like receptor protein 3, toll-like 4, total antioxidant capacity (TAC), malondialdehyde (MDA), nitrite levels measured colon PFC. Histopathological evaluations performed samples. Data analyzed t-test or one-way variance analysis. decreased increased gene markers, altered MDA, nitrite, TAC both Simultaneous induction seizure exacerbated neuroimmune response PFC colon. Results concluded that at least partially mediate comorbid decrease colitis.

Язык: Английский

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Drug-resistant epilepsy associated with peripheral complement decreases and sex-specific cytokine imbalances: a pilot study

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 11, 2025

Drug-resistant epilepsy (DRE) presents significant challenges in treatment and management. While seizure-related alterations peripheral immune players are increasingly recognized, the involvement of complement system remains insufficiently explored DRE. We studied components their relationship to cytokine profiles serum samples from 46 DRE patients 45 matched healthy controls. examined relationships between these molecules clinical outcomes, including duration, intelligence scores, age. identified DRE-associated decreases, reduced levels C1q, Factor H, C4, C4b, C3, C3b/iC3b, as well elevated bFGF. females showed dysregulation classical pathway lower TNFα interleukin-8 compared females. males exhibited classical, lectin, terminal pathways, with trends increased CCL2 CCL5 males. Specific inflammatory markers (C2, IL-8, IL-9) correlated full-scale IQ scores patients. Our study reveals significantly circulating sex-specific imbalances. These findings suggest an underlying vulnerability that may be sex-dependent warrants further investigation

Язык: Английский

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