Effect of valproate and add-on levetiracetam on inflammatory biomarkers in children with epilepsy

Labh, Rajpushpa; Gupta, Rachna; Narang, Manish; Halder, Sumita; Kar, Rajarshi

doi:10.1016/j.yebeh.2021.108358

Cited by 8 publications

(3 citation statements)

References 60 publications

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“…The possible mechanism suggested as LEVE administration prolonged the reduction of abnormal spike activity that was found to ameliorate impairment in learning and memory and fully reversed deficits in synaptic transmission as well as spasticity in the hippocampus [ 14 ]. One of the mechanisms for this action is suggested to be the reduction in the neuroinflammatory pathways in the brain’s cells [ 15 ]. Based on this information, the present study was designed to evaluate the nootropic-like activity of LEVE in DOX-induced memory defects and determine the possible mechanism by estimating the biomarker level in experimental animals using the molecular modelling approach.…”

Section: Introductionmentioning

confidence: 99%

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study

et al. 2022

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Cancer chemotherapy-induced cognitive impairment (chemobrain) is a major complication that affects the prognosis of therapy. Our study evaluates the nootropic-like activity of levetiracetam (LEVE) against doxorubicin (DOX)-induced memory defects using in vivo and molecular modelling. Rats were treated with LEVE (100 and 200 mg/kg, 30 days) and chemobrain was induced by four doses of DOX (2 mg/kg, i.p.). Spatial memory parameters were evaluated using an elevated plus maze (EPM) and Y-maze. Additionally, acetylcholinesterase (AChE) and the neuroinflammatory biomarkers cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), and tumor necrosis factor-alpha (TNF-α) were analyzed using brain homogenate. PharmMapper was used for inverse docking and AutoDock Vina was used for molecular docking. LEVE treatment significantly diminished the DOX-induced memory impairment parameters in both the EPM and Y-maze. In addition, the drug treatment significantly reduced AChE, COX-2, PGE2, NF-κB, and TNF-α levels compared to DOX-treated animals. The inverse docking procedures resulted in the identification of AChE as the potential target. Further molecular modelling studies displayed interactions with residues Gly118, Gly119, and Ser200, critical for the hydrolysis of ACh. Analysis of the results suggested that administration of LEVE improved memory-related parameters in DOX-induced animals. The ‘nootropic-like’ activity could be related to diminished AChE and neuroinflammatory mediator levels.

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Section: Introductionmentioning

confidence: 99%

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study

et al. 2022

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“…Given that our original study did not reveal a signi cant difference in TNF-alpha levels between the FS and FC groups, we hypothesize that the elevation of TNF-alpha plays a signi cant role in the pathophysiology of seizures. This assumption is also supported by the fact that TNF-alpha freely enters the central nervous system along nerve roots and secondarily increases levels of pro-in ammatory cytokines in the central nervous system [38,41].…”

Section: Discussionmentioning

confidence: 99%

IL-6 as potential predictive biomarker of febrile seizures

Papež,

Česká,

Loja

et al. 2024

Preprint

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Background Febrile seizures are the most common type of convulsions in children. Fever is induced by cytokines release during infection. Recent studies focusing on the identification of a possible role of cytokines in pathogenesis of febrile seizures have contributed conflicting results. Moreover, most of these studies investigated only a few cytokines, such as IL-1β, IL-6 and TNFα. The aim of this study was to investigate multiple cytokine-chemokine profiles that could be potentially associated with the development of febrile seizures. Methods Twenty-four febrile seizure cases (febrile seizure group) and two matched control groups were included in this study. Children with febrile illness without convulsion (febrile control group) and children without seizures and without fever (healthy control group) served as control groups. We investigated serum levels of IL-1β, IL-6, IL-8, IL-10, IL-18, CXCL10/IP-10, CCL2/MCP-1, CXCL13/BLC, TNFα, and fractalkine/CXC3CL1 in all children included in the study. Results The analysis of serum samples revealed a significant elevation of IL-6 (p = 0.0042) in the FS group compared to the febrile controls. Significantly higher levels of cytokines were also found in the FS group compared to healthy controls in IL-10 (p = 0.0039), TNFα (p = 0.0091) and MCP-1 (p = 0.0039). Conclusion Our study supports the hypothesis that IL-6 is involved in the pathogenesis of febrile seizures. We supposed that IL-6 could become a potential biomarker of the development of febrile seizures in children with febrile disease. This knowledge could be used in clinical practice to identify children at risk of developing of febrile convulsions.

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“…They did not find any significant change in the analyzed cytokines after introducing those medications. Labh et al analyzed blood MCP-1 (CCL2) and IL-1β concentrations in children with newly diagnosed epilepsy and VPA only treatment (group 1) and with epilepsy treated with both VPA and LEV as add on due to uncontrolled seizures on VPA alone (group 2) [13]. After treatment modification in both groups they observed a good response (> 50% reduction of seizures) in more than 90% of patients in both groups.…”

Section: Discussionmentioning

confidence: 99%

Immunological markers of drug resistant epilepsy and its response to immunomodulatory therapy with ACTH in children

Kaczorowska,

Czekuć-Kryśkiewicz,

Dądalski

et al. 2023

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Introduction: Drug-resistant epilepsy in infancy and childhood is a devastating condition, frequently associated with neuropsychiatric comorbidities. West syndrome is one of the most severe epilepsy syndromes. Adrenocorticotropic hormone (ACTH) treatment is recommended in such cases, but its mechanism of action is still unknown. We prospectively observed levels of selected cytokines in order to identify biomarkers of response to ACTH and the potential mechanism of its antiseizure effect. Material and methods: Fifty-three infants and young children with pharmacoresistant epilepsy receiving ACTH 1-24 were included. There were 2 control groups -children with epilepsy responding to the first medication and children with no history of epilepsy. Blood concentrations of IL-1β, IL-1Ra, IL-6, IL-8, IL-10, TNF-α, IFN-γ, MCP-1 and MIP-1α were analyzed at three time points: T0 (before ACTH), T1 (after intensive ACTH treatment) and at T2 (at the end of ACTH withdrawal). The results were correlated with the response to treatment, dose of ACTH and concomitant medications. Results: We found statistically significantly higher concentrations of IL-1, IL-8 and MIP-1α at baseline (T0) in the study group compared to the control groups. ACTH significantly lowered levels of IL-6, IFN-γ and MCP from time T0 to T1. This effect was short lasting and no significant changes in cytokine levels were found between T2 and T0. We did not find any differences in immunological markers between the responders and non-responders to ACTH. Our research did not allow us to identify any reliable immunological marker of response to ACTH treatment. We did not observe a positive effect of higher ACTH doses on the response rate in the patients. Our study showed significantly lower concentrations of IL-10 and IFN in the group of patients receiving levetiracetam. The concentration of TNF was higher and the concentration of MIP was lower in the group receiving valproic acid. Conclusions: Our study indicates that increased levels of IL-1, IL-8 and MIP-1α are associated with drug-resistant epilepsy in infants and young children and might be considered immunological markers. IL-6, IFN-γ and MCP-1 take part in the effect of ACTH. Immunological mechanisms seem also to be involved in the mechanism of action of classical antiseizure drugs.

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Effect of valproate and add-on levetiracetam on inflammatory biomarkers in children with epilepsy

Cited by 8 publications

References 60 publications

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study

IL-6 as potential predictive biomarker of febrile seizures

Immunological markers of drug resistant epilepsy and its response to immunomodulatory therapy with ACTH in children

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