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

Frontiers in Pediatrics, Journal Year: 2023, Volume and Issue: 11

Published: Nov. 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.

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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Sex-specific associations of kynurenic acid with neopterin in Alzheimer’s disease

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: July 27, 2024

Abstract Background Sex differences in neuroinflammation could contribute to women’s increased risk of Alzheimer’s disease (AD), providing rationale for exploring sex-specific AD biomarkers. In AD, dysregulation the kynurenine pathway (KP) contributes and there is some evidence sex KP metabolism. However, associations between metabolism biomarkers need be explored further. Methods Here we investigate cerebrospinal fluid concentrations seven metabolites with established neopterin, an indicator neuroinflammation. This study included 311 patients symptomatic 105 age-matched cognitively unimpaired (CU) controls, followed up 5 years. Results We found group, higher levels most men, while were no CU group. line this, more significantly altered men compared was a trend same direction women. Furthermore, kynurenic acid acid/quinolinic ratio but clinical progression. Discussion our cohort, restricted patients. Our results suggest that due inflammation

Language: Английский

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Dysregulation of the kynurenine pathway is related to persistent cognitive impairment in tick-borne encephalitis

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Characterizing circulating biomarkers for childhood dementia disorders: A scoping review of clinical trials

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00546 - e00546

Published: Feb. 1, 2025

Childhood dementias, a group of neurological disorders are characterised by neurocognitive decline, with physical and psychosocial impacts for individuals. With therapy available <5 ​% childhood there is high level unmet need. Integration biomarkers in clinical trials important to characterize distinctive biological activities interrogate targets therapeutic development. This study reviewed four trial registries examine circulating dementias. Findings from 262 studies were synthesized across 49/72 (68 ​%) dementia disorders. Disease-related associated 1) the primary pathophysiology 2) downstream pathogenic events 3) drug-related pharmacokinetics, safety and/or tolerability. The predominant measures metabolites linked pathophysiological pathway (102 measures, 185 studies), while use cytoskeletal proteins (3 15 inflammatory mediators (19 24 oxidative stress-related analytes (15 8 neurotransmitters or related neuro-metabolites 5 studies) limited. A range potential used trials; however, their inconsistent under utilised among conditions. Development panel has link shared pathways heterogeneity dementias exert significant impact development disease-modifying therapies.

Language: Английский

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Inflammatory Markers in the Blood of Spastic Cerebral Palsy Children: A Case–Control Study

Children, Journal Year: 2025, Volume and Issue: 12(3), P. 343 - 343

Published: March 9, 2025

Objectives: The aim was to simultaneously investigate inflammatory biomarkers, neopterin, the kynurenine/tryptophan (Kyn/Trp) pathway, vitamin D (VitD), binding protein (VDBP), and erythrocyte folate, in cerebral palsy (CP). Methods: A case–control study conducted at Mersin University Hospital. Three- ten-year-old patients with spastic CP (n = 50) age- gender-matched healthy controls 55) were included. Serum levels of Trp, Kyn 25OHD, plasma VDBP, folate concentrations measured. Indoleamine-2,3-dioxygenase 1 (IDO-1) enzyme activity evaluated according Kyn/Trp ratio. Comparison correlation analyses performed. Results: lower children than (p 0.037, p < 0.001, 0.003, respectively). IDO1 not significantly different between control groups 0.214). VitD VDBP higher 0.001 level also 0.001). No significant found age biomarkers group. Neopterin correlated Gross Motor Function Classification System (GMFCS) (r 0.292, 0.044), while there no other GMFCS Conclusions: Inflammatory neopterin are lower, higher, anti-inflammatory is compared children. More knowledge needed demonstrate status CP.

Language: Английский

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Tryptophan metabolism in migraine: a review of experimental and clinical studies and a need to enhance research strategies

Reviews in the Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Abstract Tryptophan (TRP) metabolism produces various neuroactive substances in the gastrointestinal tract, as well central and peripheral nervous systems intestinal microbiota. Initially centered on serotonin pathway TRP itself, many studies are now focusing kynurenine pathway, with an increasing interest indole pathway. Several metabolites have been associated migraines, suggesting that may serve a potential therapeutic target. However, these significant limitations, including small number of participants, lack standardized diets prior to and/or during clinical trials, insufficient information regarding transformation after its intake. Furthermore, no thorough study encompasses all essential components metabolism: products, enzymes, receptors, transporters. Different mechanisms explain involvement glutamate signaling neurovasodilatory, immune, oxidative, inflammatory processes. The results role migraine be helpful for making dietary recommendations prevention management; however, individual characteristics metabolizing should considered. aim this narrative perspective review is critically present explore their implications therapy. Unlike other reviews focus solely either or our paper addresses three primary pathways.

Language: Английский

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Low serum neopterin early indicates durable benefits of atezolizumab and pembrolizumab therapy in advanced lung cancer

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 16, 2025

Language: Английский

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Parkinson’s disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 26, 2025

Abstract Recent studies demonstrate that Parkinson’s disease (PD) is associated with dysregulated metabolic flux through the kynurenine pathway (KP), in which tryptophan converted to (KYN), and KYN subsequently metabolized neuroactive compounds quinolinic acid (QA) kynurenic (KA). Here, we used mass-spectrometry compare blood cerebral spinal fluid (CSF) KP metabolites between 158 unimpaired older adults 177 participants PD. We found increased neuroexcitatory QA/KA ratio both plasma CSF of PD peripheral inflammation vitamin B 6 deficiency. Furthermore, QA tracked tau, soluble TREM2 (sTREM2) severity motor non-motor clinical symptoms. Finally, patient subgroups distinct profiles displayed features. These data validate as a site brain periphery crosstalk, integrating B-vitamin status, metabolism ultimately influence manifestation.

Language: Английский

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Untargeted metabolomics reveals key metabolic alterations in pediatric epilepsy with insights into Tryptophan metabolism and the gut–brain axis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 30, 2025

Language: Английский

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