Therapeutic Strategies to Ameliorate Neuronal Damage in Epilepsy by Regulating Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(5), P. 784 - 784

Published: May 11, 2023

Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development new therapeutic strategies against could be beneficial. Oxidative stress mitochondrial dysfunction are frequently observed in epilepsy. Additionally, neuroinflammation increasingly understood contribute pathogenesis Mitochondrial also recognized for its contributions neuronal excitability apoptosis, which can lead loss This review focuses on roles oxidative damage, dysfunction, NAPDH oxidase, blood–brain barrier, excitotoxicity, We therapies used treat prevent seizures, including anti-seizure medications, anti-epileptic drugs, anti-inflammatory therapies, antioxidant therapies. In addition, we use neuromodulation surgery treatment Finally, present role dietary nutritional management epilepsy, ketogenic diet intake vitamins, polyphenols, flavonoids. By reviewing available interventions research pathophysiology this points areas further manage

Language: Английский

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Brain energy metabolism: A roadmap for future research

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: 168(5), P. 910 - 954

Published: Jan. 6, 2024

Although we have learned much about how the brain fuels its functions over last decades, there remains still to discover in an organ that is so complex. This article lays out major gaps our knowledge of interrelationships between metabolism and function, including biochemical, cellular, subcellular aspects functional imaging adult brain, as well during development, aging, disease. The focus on unknowns substrates associated transporters, roles insulin lipid droplets, emerging role microglia, mysteries cofactor signaling molecule NAD

Language: Английский

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

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(5), P. 334 - 350

Published: March 26, 2024

Language: Английский

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Exploring the potential of the ketogenic diet in autism spectrum disorder: metabolic, genetic, and therapeutic insights

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(1)

Published: Jan. 8, 2025

Abstract Current treatment approaches for Autism spectrum disorder (ASD) primarily focus on symptom management rather than addressing underlying dysfunctions. The ketogenic diet (KD), a high-fat, low-carbohydrate inducing nutritional ketosis, has shown promise in treating epilepsy and may offer therapeutic benefits ASD by modulating metabolic neuroprotective pathways. This review examined the potential impact of KD mechanisms ASD. While evidence from human studies is limited, animal research large overlap modulated dysfunctions As such, targeting multiple disrupted pathways at once, presents multifaceted approach However, more needed effectiveness modulation Additionally, precision medicine could help identify individuals who would benefit most intervention, potentially extending its use to other psychiatric conditions with similar patterns. Consequently, interventions might show induce drastic paradigm shift understanding

Language: Английский

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Glial Glutamine Homeostasis in Health and Disease

Neurochemical Research, Journal Year: 2022, Volume and Issue: 48(4), P. 1100 - 1128

Published: Nov. 2, 2022

Language: Английский

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Astrocyte-neuron circuits in epilepsy

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 179, P. 106058 - 106058

Published: March 1, 2023

The epilepsies are a diverse spectrum of disease states characterized by spontaneous seizures and associated comorbidities. Neuron-focused perspectives have yielded an array widely used anti-seizure medications able to explain some, but not all, the imbalance excitation inhibition which manifests itself as seizures. Furthermore, rate pharmacoresistant epilepsy remains high despite regular approval novel medications. Gaining more complete understanding processes that turn healthy brain into epileptic (epileptogenesis) well generate individual (ictogenesis) may necessitate broadening our focus other cell types. As will be detailed in this review, astrocytes augment neuronal activity at level neurons form gliotransmission tripartite synapse. Under normal conditions, essential maintenance blood-brain barrier integrity remediation inflammation oxidative stress, these functions impaired. Epilepsy results disruptions way relate each gap junctions has important implications for ion water homeostasis. In their activated state, contribute imbalances excitability due decreased capacity take up metabolize glutamate increased adenosine. adenosine metabolism, DNA hypermethylation epigenetic changes underly epileptogenesis. Lastly, we explore potential explanatory power astrocyte function detail specific context comorbid occurrence Alzheimer's disruption sleep-wake regulation with both conditions.

Language: Английский

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Properties of REM sleep alterations with epilepsy

Brain, Journal Year: 2023, Volume and Issue: 146(6), P. 2431 - 2442

Published: March 3, 2023

Abstract It is usually assumed that individuals rest during sleep. However, coordinated neural activity presumably requires high energy consumption increased REM Here, using freely moving male transgenic mice, the local brain environment and astrocyte sleep were examined fibre photometry method with an optical inserted deep into lateral hypothalamus, a region linked controlling metabolic state of entire brain. Optical fluctuations endogenous autofluorescence parenchyma or fluorescence sensors for Ca2+ pH expressed in astrocytes examined. Using newly devised analysis, changes cytosolic blood volume (BBV) extracted. On sleep, astrocytic decreases, decreases (acidification) BBV increases. Acidification was unexpected, as increase would result efficient carbon dioxide and/or lactate removal, which leads to alkalinization environment. could be glutamate transporter due enhanced neuronal aerobic metabolism astrocytes. Notably, signal preceded onset electrophysiological property signature by ∼20–30 s. This suggests have strong control over cell activity. With repeated stimulation hippocampus, seizure response gradually develops through kindling. After fully kindled obtained multiple days stimuli, properties at hypothalamus again. Although negative deflection detected observed after kindling, estimated component changed. The decrease minimal, large emerged. acidic shift may trigger additional gliotransmitter release from astrocytes, lead hyperexcitable As change development epilepsy, analysis serve biomarker epileptogenesis severity. also predict whether specific episode triggers post-sleep seizures.

Language: Английский

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ROS/Electro Dual-Reactive Nanogel for Targeting Epileptic Foci to Remodel Aberrant Circuits and Inflammatory Microenvironment

ACS Nano, Journal Year: 2023, Volume and Issue: 17(8), P. 7847 - 7864

Published: April 11, 2023

Medicinal treatment against epilepsy is faced with intractable problems, especially epileptogenesis that cannot be blocked by clinical antiepileptic drugs (AEDs) during the latency of epilepsy. Abnormal circuits neurons interact inflammatory microenvironment glial cells in epileptic foci, resulting recurrent seizures and refractory Herein, we have selected phenytoin (PHT) as a model drug to derive ROS-responsive consuming prodrug, which combined an electro-responsive group (sulfonate sodium, SS) focus-recognizing (α-methyl-l-tryptophan, AMT) form hydrogel nanoparticles (i.e., nanogel). The nanogel will target release PHT response high concentration reactive oxygen species (ROS) microenvironment, inhibit overexcited circuits. Meanwhile, clearance ROS, can also reduce oxidative stress alleviate inflammation. Thus, synergistic regulation lesions achieved. Our expected provide more comprehensive strategy for treatment.

Language: Английский

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Metabolomic changes in adults with status epilepticus: A human case–control study

Epilepsia, Journal Year: 2024, Volume and Issue: 65(4), P. 929 - 943

Published: Feb. 10, 2024

Abstract Objective Status epilepticus (SE) is a life‐threatening prolonged epileptic seizure that affects ~40 per 100 000 people yearly worldwide. The persistence of seizures may lead to excitotoxic processes, neuronal loss, and neuroinflammation, resulting in long‐term neurocognitive functional disabilities. A better understanding the pathophysiological mechanisms underlying SE consequences crucial for improving management preventing secondary injury. Methods We conducted comprehensive untargeted metabolomic analysis, using liquid chromatography coupled with high‐resolution mass spectrometry (LC‐HRMS), on plasma cerebrospinal fluid (CSF) samples from 78 adult patients 107 control without SE, including 29 CSF both groups. fingerprints were compared between controls. Metabolites differences relative abundances could not be attributed treatment or nutrition provided intensive care unit isolated. Enrichment analysis was performed these metabolites identify most affected pathways. Results identified 76 37 exhibited differential expression enrichment revealed metabolic dysregulations primarily amino acid metabolism (including glutamate, alanine, tryptophan, glycine, serine metabolism), pyrimidine metabolism, lipid homeostasis. Specifically, had elevated levels pyruvate, quinolinic acid, keto butyric levels, along lower arginine, N ‐acetylaspartylglutamate (NAAG), uracil, uridine. tryptophan kynurenine pathway as significantly altered overproduction an ‐methyl‐ d ‐aspartate (NMDA) receptor agonist pro‐inflammatory properties. Significance This study has several pathways play pivotal roles consequences, such pathway. These findings offer novel perspectives development neuroprotective therapeutics.

Language: Английский

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Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Nov. 19, 2024

Abstract Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons poses great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it urgent need explore other potential mechanism develop novel approach delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), versatile epigenetic regulators responsible gene transcription via binding histones or non-histone substrates, have grabbed considerable attention in drug discovery. There also substantial evidences supporting aberrant expressions and/activities HDAC isoforms reported epilepsy inhibitors (HDACi) been purposes this condition. However, specific mechanisms underlying role HDACs progression not fully understood. Herein, we reviewed basic information HDACs, summarized recent findings associated with roles diverse subunits discussed regulatory which affected development epilepsy. Additionally, provided brief discussion on as promising targets treatment, serving valuable reference study clinical translation field.

Language: Английский

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