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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Modification of Neural Circuit Functions by Microglial P2Y6 Receptors in Health and Neurodegeneration

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 14, 2024

Abstract Neural circuits consisting of neurons and glial cells help to establish all functions the CNS. Microglia, resident immunocytes CNS, are endowed with UDP-sensitive P2Y6 receptors (P2Y6Rs) which regulate phagocytosis/pruning excessive synapses during individual development refine in an activity-dependent manner adulthood. In addition, this type receptor plays a decisive role primary (Alzheimer’s disease, Parkinson’s neuropathic pain) secondary (epilepsy, ischemic-, mechanical-, or irradiation-induced) neurodegeneration. A whole range microglial cytokines controlled by P2Y6Rs, such as interleukins IL-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α), leads neuroinflammation, resulting Hence, small molecular antagonists P2Y6Rs genetic knockdown provide feasible ways alleviate inflammation-induced neurological disorders but might also interfere regulation synaptic circuitry. The present review aims at investigating dual microglia, both shaping neural targeted phagocytosis promoting neurodegenerative illnesses fostering neuroinflammation through multiple transduction mechanisms.

Язык: Английский

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Systems Pharmacology Approach and Experiment Evaluation Reveal Pterocarpus Mildbraedii (Fabaceae) Intervention for Counteracting Behavioral Changes and Neuroinflammatory and Oxidative Stress Markers Against Lps-Induced Alzheimer's Disease in Rats

Опубликована: Янв. 1, 2025

Ethnopharmacological relevance: Pterocarpus mildbraedii was believed to have multiple benefits, including antioxidant, antipyretic, antalgic, anti-convulsant, and anxiolytic effects. Previous studies reported that water extract (Pm) contained secondary metabolites able cross the BBB. However, Pm's systemic mechanism targets for neuroinflammation remain largely unexplored.Aim of study: This research used a systems pharmacology approach experiment evaluation reveal potential protective effects Pm against neuroinflammation, oxidative stress, behavioral changes in an LPS-induced Alzheimer's disease (AD) rat model.Materials methods: integrated network analysis experimental verification evaluate pharmacological PM AD systematically. Swiss Target Prediction, GeneCards, STRING databases were employed identify targets. The interaction between active components hub confirmed via molecular docking. GO KEGG pathway analyses also carried out. Further, vitro bioassays explore anti-inflammatory antioxidant activities and, finally, vivo neuroinflammatory stress markers.Results: Network docking revealed primarily regulates signaling pathways such as ESR1, ESR2, BACE1, MAPK1, TLR4, IL6, GSK3B through like liquiritigenin pterocarptriol. identified significant action AD, nitrogen metabolism VEGF pathway. In vitro, demonstrated their properties, along with inhibitory on AchE BchE. Behavioral tests showed LPS exposure impaired exploratory behavior, spatial learning, increased anxiety rats, correlating brain, marked by elevated MDA NO levels, decreased CAT, SOD, GSH levels. raised TNF-α IL-6 levels while reducing dopamine, serotonin, AChE activity. Notably, treatment significantly mitigated improved activity, restored neurotransmitter animals.Conclusion: paper established P. could inhibit its components, targets, pathways. milbraedii may be candidate treatment.

Язык: Английский

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Integrated Mendelian Randomization and Single‐Cell Transcriptomics Analysis Identifies Critical Blood Biomarkers and Potential Mechanisms in Epilepsy

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(1)

Опубликована: Янв. 1, 2025

ABSTRACT Background Epilepsy has a genetic predisposition, yet causal factors and the dynamics of immune environment in epilepsy are not fully understood. Methods We analyzed peripheral blood samples from patients, identifying key genes associated with risk through Mendelian randomization, using eQTLGen genome‐wide association studies. The environment's composition was explored CIBERSORT. An mouse model established to validated expression at transcriptomic proteomic levels single‐cell analysis. Relevant pathways were verified. Finally, we developed predictive for antiepileptic drug response patients. Results found that CDC25B , DNMT1 GZMA MTX1 SSH2 decreases risk, whereas FGD3 RAF1 SH3BP5L increase it. patients exhibited an altered profile, notably increased activated mast cells decreased CD4 memory T γδ cells. Eight significantly related this environment. In animal model, upregulated both mRNA protein hippocampus. specifically elevated microglia primarily actin regulation. trained deployed on online platform. Conclusions This study elucidates linked epilepsy, delineates landscape, highlights interaction between these domains, providing insights into potential mechanisms treatments.

Язык: Английский

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The Role of Glial Cells in the Pathophysiology of Epilepsy

Cells, Год журнала: 2025, Номер 14(2), С. 94 - 94

Опубликована: Янв. 10, 2025

Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly impacting individuals worldwide. Current treatments are often ineffective for third of patients and can cause severe side effects, necessitating new therapeutic approaches. Glial cells, particularly astrocytes, microglia, oligodendrocytes, emerging as crucial targets in epilepsy management. Astrocytes regulate neuronal homeostasis, excitability, synaptic plasticity, playing key roles maintaining the blood-brain barrier (BBB) mediating neuroinflammatory responses. Dysregulated astrocyte functions, such reactive astrogliosis, lead to abnormal activity seizure generation. They release gliotransmitters, cytokines, chemokines that may exacerbate or mitigate seizures. Microglia, innate immune cells CNS, contribute neuroinflammation, glutamate excitotoxicity, balance between excitatory inhibitory neurotransmission, underscoring their dual role promotion protection. Meanwhile, primarily involved myelination, also modulate axonal excitability neuron-glia network underlying pathogenesis. Understanding dynamic interactions glial with neurons provides promising avenues novel therapies. Targeting these improved control better clinical outcomes, offering hope refractory epilepsy.

Язык: Английский

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Investigation of the relationship between Body Mass Index and epilepsy

Epilepsy & Behavior, Год журнала: 2025, Номер 165, С. 110295 - 110295

Опубликована: Фев. 28, 2025

Язык: Английский

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Galbanic acid delays the development of seizures by modulating the expression of TNFα, IL1β, and TLR4 genes and reducing hippocampal nitrite levels and may be useful in the treatment of epilepsy

Neuroscience Letters, Год журнала: 2025, Номер unknown, С. 138200 - 138200

Опубликована: Март 1, 2025

Язык: Английский

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Immunological factors in pediatric generalized and focal epilepsy: interplay with anti-seizure medications

BMC Pediatrics, Год журнала: 2025, Номер 25(1)

Опубликована: Март 17, 2025

Pediatric epilepsy presents challenges in treatment optimization, with a significant proportion of patients experiencing inadequate seizure control despite anti-seizure medications (ASMs) therapy. Recent research has indicated the involvement neuroinflammation and immune-mediated mechanisms pathogenesis, suggesting potential interplay between immunological factors ASMs responsiveness. This study aimed to investigate role pediatric generalized, focal their interaction understand influence on outcomes. A retrospective cohort was conducted involving 136 patients, categorized into Anti-seizure Insensitive Group (n = 67) Sensitive 69). Immunoglobulin levels factors, including cytokines, were assessed before treatment. Seizure characteristics also analyzed. Associations characteristics, sensitivity evaluated. The revealed differences interleukin-6 (IL-6), IL-1β IL-10 levels, insensitive sensitive groups. Furthermore, frequency, drug-resistant seizures, severity, seizure-free period, status epilepticus all demonstrated correlations ASMs, negative for positive period epilepticus. highlights complex immune function, mechanisms, underscoring need comprehensive understanding modulation drug response epilepsy. Not applicable.

Язык: Английский

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Reparixin as a Potential Antiepileptogenic Agent: Modulation of the CXCL1–CXCR1/2 Axis and Seizure Activity in a Kindling Rat Model of Temporal Lobe Epilepsy

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2831 - 2831

Опубликована: Март 21, 2025

Chemokine (CXC motif) ligand 8 (CXCL8) is a pro-inflammatory chemokine binding to CXC motif receptors 1/2 (CXCR1/2). Patients with temporal lobe epilepsy (TLE) exhibit increased serum CXCL8 levels. 1 (CXCL1), murine ortholog of CXCL8, has been implicated in seizure generation and neuronal loss. This study evaluated the antiepileptogenic antiseizure effects reparixin amygdaloid kindling rat model TLE. Reparixin was administered during period for 14 days, seizures were induced twice daily via electrical stimulation. To assess effects, fully kindled animals, stimulations performed 24 48 h later. Levetiracetam, broad-spectrum drug, intraperitoneally (i.p.) as positive control before each delayed secondary generalization kindling. reduced severity after-discharge duration animals at from treatment initiation. CXCR1/2 protein kinase B pathway proteins exhibited no significant changes; phospho-extracellular signal-regulated (pERK)/ERK ratio cortex hippocampus. CXCL1 expression significantly decreased cortex. partial by modulating CXCL1–CXCR1/2 axis reducing ERK signaling. Already clinical trials on respiratory diseases, could be repurposed therapy.

Язык: Английский

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Mechanistic insights into the sleep-glymphopathy-cerebral small vessel disease loop: implications for epilepsy pathophysiology and therapy

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Март 27, 2025

Epilepsy is the second most common neurological disorder and affects approximately 50 million people worldwide. Despite advances in antiepileptic therapy, about 30% of patients develop refractory epilepsy. Recent studies have shown sleep, glymphatic function, cerebral small vessel disease (CSVD), epilepsy are interrelated by sharing a multidirectional relationship influencing their severity progression. Sleep plays vital role brain homeostasis promotes clearance responsible for removal metabolic wastes neurotoxic substances from brain. Disrupted sleep feature can lead to impairment efficiency or glymphopathy, promoting neuroinflammation accrual epileptogenic factors. CSVD, occurring up 60% aging population, further exacerbates neurovascular compromise neurodegeneration increasing seizure susceptibility worsening outcomes. This narrative review aims discuss molecular pathophysiological inter-relationships between these factors, providing new framework that places glymphopathy CSVD as contributors epileptogenesis conditions disruption. We propose an integrative model wherein vascular insufficiency interact positive feedback loop disruption increased vulnerability mediated epileptic activity. Acknowledging interactions has significant impacts on both research clinical practice. Targeting modulation, cerebrovascular health presents promising avenue therapeutic intervention. Future should focus developing precision medicine approaches integrate neuro-glial-vascular mechanisms optimize management. Clinically, addressing disturbances may improve treatment effectiveness, reduce burden, overall highlights need interdisciplinary break vicious cycle epilepsy, disturbance, pathology, paving way innovative paradigms.

Язык: Английский

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