The Role of Neuroinflammation and Network Anomalies in Drug-Resistant Epilepsy

Neuroscience Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought play role in such cases. Despite being long-debated issue the field DRE, mechanisms underlying neuroinflammation have yet be fully elucidated. The pro-inflammatory microenvironment within brain tissue with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells cytokines nervous system can lead extensive biochemical changes, as connexin hemichannel excitability disruption neurotransmitter homeostasis. presence inflammation may give rise neuronal network abnormalities suppress endogenous antiepileptic systems. We focus on anomalies from multiple perspectives identify critical points clinical application. hope provide an insightful overview advance quest better treatments.

Language: Английский

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Immune Cell-NSPC Interactions: Friend or Foe in CNS Injury and Repair?

Differentiation, Journal Year: 2025, Volume and Issue: 143, P. 100855 - 100855

Published: March 15, 2025

Language: Английский

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The Putative Role of Neuroinflammation in the Interaction between Traumatic Brain Injuries, Sleep, Pain and Other Neuropsychiatric Outcomes: A State-of-the-Art Review

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(5), P. 1793 - 1793

Published: Feb. 23, 2023

Sleep disturbances are widely prevalent following a traumatic brain injury (TBI) and have the potential to contribute numerous post-traumatic physiological, psychological, cognitive difficulties developing chronically, including chronic pain. An important pathophysiological mechanism involved in recovery of TBI is neuroinflammation, which leads many downstream consequences. While neuroinflammation process that can be both beneficial detrimental individuals' after sustaining TBI, recent evidence suggests may worsen outcomes traumatically injured patients, as well exacerbate deleterious consequences sleep disturbances. Additionally, bidirectional relationship between has been described, where plays role regulation and, turn, poor promotes neuroinflammation. Given complexity this interplay, review aims clarify with an emphasis on long-term such pain, mood disorders, dysfunctions, elevated risk Alzheimer's disease dementia. In addition, some management strategies novel treatment targeting will discussed order establish effective approach mitigate TBI.

Language: Английский

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Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 816 - 816

Published: May 11, 2023

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning knowledge that disease intimately tied to neurodegenerative disorders, affecting both central and peripheral nervous systems well leading dementia, seventh cause of death. New innovative therapeutic strategies address metabolism, apoptosis, autophagy, pyroptosis, mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), risk factors apolipoprotein E (APOE-ε4) gene coronavirus 2019 (COVID-19) can offer valuable insights for clinical care treatment disorders impacted by disease. Critical insight into modulation these complex pathways are required since mTOR pathways, AMPK activation, improve memory retention in Alzheimer's (AD) DM, promote healthy aging, facilitate clearance β-amyloid (Aß) tau brain, control inflammation, but also may lead cognitive loss long-COVID syndrome through mechanisms include oxidative stress, mitochondrial cytokine release, APOE-ε4 if autophagy other programmed cell death left unchecked.

Language: Английский

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Signaling pathways in brain ischemia: Mechanisms and therapeutic implications

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 251, P. 108541 - 108541

Published: Oct. 1, 2023

Language: Английский

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Dexmedetomidine attenuates sleep deprivation-induced inhibition of hippocampal neurogenesis via VEGF-VEGFR2 signaling and inhibits neuroinflammation

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115085 - 115085

Published: June 29, 2023

Long periods of sleep deprivation (SD) have serious effects on health. While the α2 adrenoceptor agonist dexmedetomidine (DEX) can improve quality for patients who insomnia, effect DEX cognition and mechanisms after SD remains elusive. C57BL/6 mice were subjected to 20 h daily seven days. (100 μg/kg) was administered intravenously twice (at 1:00 p.m. 3:00 p.m.) during days SD. We found that systemic administration attenuated cognitive deficits by performing Y maze novel object recognition tests increased DCX+, SOX2+, Ki67+, BrdU+NeuN+/NeuN+ cell numbers in dentate gyrus (DG) region using immunofluorescence, western blotting, BrdU staining. did not reverse decrease or Ki67+ α2A-adrenoceptor antagonist BRL-44408. Furthermore, vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) expression upregulated SD+DEX compared with mice. Luminex analysis showed neurogenic possibly related inhibition neuroinflammation, including IL-1α, IL-2, CCL5, CXCL1. Our results suggested alleviated impaired learning memory potentially inducing hippocampal neurogenesis via VEGF-VEGFR2 signaling pathway suppressing α2A adrenoceptors are required This mechanism may add our knowledge clinical treatment caused

Language: Английский

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The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 8, 2023

Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1

Language: Английский

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The Effects of Extrinsic and Intrinsic Factors on Neurogenesis

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1285 - 1285

Published: April 29, 2023

In the mammalian brain, neurogenesis is maintained throughout adulthood primarily in two typical niches, subgranular zone (SGZ) of dentate gyrus and subventricular (SVZ) lateral ventricles other nonclassic neurogenic areas (e.g., amygdala striatum). During prenatal early postnatal development, neural stem cells (NSCs) differentiate into neurons migrate to appropriate such as olfactory bulb where they integrate existing networks; these phenomena constitute multistep process neurogenesis. Alterations any processes impair may even lead brain dysfunction, including cognitive impairment neurodegeneration. Here, we first summarize main properties niches describe cellular molecular mechanisms Accumulating evidence indicates that plays an integral role neuronal plasticity cognition period. Given can be highly modulated by a number extrinsic intrinsic factors, discuss impact alcohol) hormones) modulators on Additionally, provide overview contribution severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection persistent neurological sequelae neurodegeneration, defects accelerated cell death. Together, our review provides link between extrinsic/intrinsic factors explains possible abnormal underlying disorders.

Language: Английский

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Activation of the CD200/CD200R1 axis improves cognitive impairment by enhancing hippocampal neurogenesis via suppression of M1 microglial polarization and neuroinflammation in hypoxic-ischemic neonatal rats

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 128, P. 111532 - 111532

Published: Jan. 21, 2024

Following hypoxic-ischemic brain damage (HIBD), there is a decline in cognitive function; however, are no effective treatment strategies for this condition neonates. This study aimed to evaluate the role of cluster differentiation 200 (CD200)/CD200R1 axis function following HIBD using an established model postnatal day 7 rats. Western blotting analysis was conducted protein expression levels CD200, CD200R1, proteins associated with PI3K/Akt-NF-κB pathway, and inflammatory factors such as TNF-α, IL-1β, IL-6 hippocampus. Additionally, double-immunofluorescence labeling utilized M1 microglial polarization neurogenesis To assess learning memory experimental rats, Morris water maze (MWM) test conducted. leads decrease CD200 CD200R1 neonatal rat hippocampus, while simultaneously increasing IL-6, IL-1β proteins, ultimately resulting impairment. The administration CD200Fc, fusion found enhance p-PI3K p-Akt, but reduce p-NF-κB. CD200Fc inhibited microglia, reduced neuroinflammation, improved hippocampal neurogenesis, mitigated impairment caused by In contrast, blocking interaction between anti-CD200R1 antibody (CD200R1 Ab) exerted opposite effect. Furthermore, PI3K specific activator, 740Y-P, significantly increased p-NF-κB expression. It also rats HIBD. Our findings illustrate that activation CD200/CD200R1 inhibits NF-κB-mediated microglia improve HIBD-induced disorder via PI3K/Akt signaling pathway.

Language: Английский

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cAMP-PKA signaling pathway and anxiety: Where do we go next?

Cellular Signalling, Journal Year: 2024, Volume and Issue: 122, P. 111311 - 111311

Published: July 24, 2024

Language: Английский

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