Asymmetrical glymphatic dysfunction in patients with Long Covid associated neurocognitive impairment- Correlation with BBB disruption

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

Background and Purpose The glymphatic system, a waste clearance pathway, has been implicated in several neurological conditions associated with neuroinflammation. COVID-19 neurocognitive impairment, part of the post-acute sequelae SARS-CoV-2 infection (PASC), is strongly neuroinflammation disrupted blood-brain barrier (BBB). Several studies have synergistic interaction between system dysfunction BBB disruption. In this proof-of-concept study, we investigated relationship diffusion along perivascular spaces DTI (DTI-ALPS) increased capillary permeability metric- K trans derived from DCE perfusion patients PASC. Materials Methods 14 subjects PASC who had persisting symptoms anosmia, ageusia, fatigue, cognitive impairment (CI) ten healthy age sex matched controls were recruited. All underwent routine advanced MR imaging early at two time points, (3 months +/- 2 weeks) referred as Time Point 1 (TP-1) 10 repeated MRI scan 12 (+/- after (TP-2), while done only TP-1. elaborate assessment. final analysis included those study both points (n-10). addition to anatomical imaging. Statistical analysis Given small size sample nonnormality data descriptive analyses, nonparametric analyses used for group comparisons. A two-sample Wilcoxon rank sum test was show differences DTI-ALPS predefined ROI. Spearman’s correlation coefficient (rho) assess K-trans index. Results There significant reduction index left hemisphere (z=2.04, p < 0.04). However, there no change over strong inverse central white matter (rho=0.66, p< 0.03). Conclusion Our suggests that disruption disordered drainage may contribute neuroaxonal injury PASC, could serve powerful non-invasive biomarker.

Language: Английский

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Lipid Therapy for Dyslipidemic Disorders Activates 21st Century Nano Antioxidant Hydrogen as a Potential Anti-COVID-19 Agent: Review

Special journal of the Medical Academy and other Life Sciences, Journal Year: 2023, Volume and Issue: 1(7)

Published: Aug. 27, 2023

According to the World Health Organization (WHO), coronavirus infection (COVID-19, (COronaVIrus Disease 2019) is an infectious disease caused by SARS-CoV-2 virus [1]. virus, Severe Acute Respiratory Syndrome-related 2. Initially considered pulmonary - respiratory pathology, then it turned out be poly-systemic, with multi-inflammation of many other organs, and central nervous system. Multisystem inflammatory syndrome in adults (MIS-A) [2], liver [3]. In pediatrics children (MIS-C) or PMIS-TS (Pediatric MIS temporarily associated infection) [4,5], SARS-COV-2/ COVID-19 induce Kawasaki-Like [6]. Neurological manifestations [7], recurrence meningitis without involvement [8]. Brain damage COVID primarily neurological, as a material signaling pathway COVID-infection cerebral vessels. This important, from release these patients, additional stress, suffering, stigmatization society, their isolation, intimidation, coercion (bullying) violation restriction rights. Since, concomitantly lesions cognitive deficits are component post-acute consequences (PASC), where role kynurenine significant temporary impairment [9]. The main for breakdown tryptophan amino acid, which synthesis serotonin impossible, controls cycles sleep wakefulness, precursor hormone melatonin patients COVID-19, imbalance T-helpers 1 2 leads cytokine storm that can contribute myocardial [10]. conditioned immunocompromising (IC) CHAOS [C]ardiovascular Compromise: shock; [H]omeostasis; [A]poptosis; [O]rgan Dysfunction; [S]uppression Immune System development Systemic response (SIRS) Multiple Organ Dysfunction Syndrome (MODS) [11,12]. With pronounced multiple symptoms: Electro Ion Membrane Distress (Syndrome Maria & Irina Vasilieva) [13,14] membrane electrical electromembrane paralysis; Capillary Leak Syndrome; Microcirculatory-Mitochondrial Syndrom [15,16]. Also described: Overlap mechanisms transient global amnesia [17]; Hypokalemia-stroke mimic [18]; Differential diagnosis cacosmia dysgeusia pandemic [19].

Language: Английский

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Improvement of immune dysregulation and health-related quality of life in individuals with long COVID at 24-months following SARS-CoV-2 infection

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 28, 2023

ABSTRACT This study investigated the humoral and cellular immune responses in individuals with long COVID (LC) compared to age gender matched recovered COVID-19 controls (MC) over 24-months. LC participants showed elevated spike nucleocapsid IgG levels, higher neutralizing capacity, increased spike- nucleocapsid-specific CD4+ T cells, PD-1, TIM-3 expression on CD8+ cells at 3- 8-months, but these differences did not persist Some had detectable IFN-γ IFN-β, that was attributed reinfection antigen re-exposure. Single-cell RNA sequencing 24-month timepoint revealed similar cell proportions reconstitution of naïve B subsets LC. No significant exhaustion scores or antigen-specific clones were observed. These findings suggest resolution activation return comparable between MC time. Improvement self-reported health-related quality life 24-months also evident majority (62%). PTX3, CRP levels platelet count associated improvements life.

Language: Английский

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Activation of the kynurenine pathway identified in individuals with covert hepatic encephalopathy

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(12)

Published: Nov. 14, 2024

Background: HE is a neuropsychiatric complication of liver disease characterized by systemic elevation in ammonia and proinflammatory cytokines. These neurotoxins cross the blood-brain barrier cause neuroinflammation, which can activate kynurenine pathway (KP). This results dysregulated production neuroactive KP metabolites, such as quinolinic acid, known to astrocyte neuronal death. Our aim was compare activity between patients with covert (CHE), without encephalopathic cirrhosis (NHE), healthy controls (HCs). Methods: single-center prospective cohort study conducted 2018 2021 at St Vincent’s Hospital, Sydney. Overall, 13 CHE, 10 NHE, 12 HC were recruited. Patients diagnosed CHE if they scored ≤−4 on Psychometric Hepatic Encephalopathy Score. metabolite levels quantified plasma samples via HPLC gas chromatography/mass spectrometry. One-way Kruskal-Wallis test used expression enzymes. Results: highly activated cirrhosis, demonstrated higher rate-limiting enzymes, indoleamine 2,3-dioxygenase, tryptophan-2,3-dioxygenase both (65.04±20.72, p =0.003) NHE (64.85±22.10, =0.015) compared (40.95±7.301). Higher acid concentrations (3726 nM±3385, <0.001) (1788 nM±632.3, =0.032) (624 nM±457). activation positively correlated inflammatory marker C-reactive protein (R s =0.721, ≤0.01). Conclusions: resulting heightened neurotoxic metabolites. Dysregulation demonstrable who do not yet show clinical signs neurocognitive impairment. Therapeutic agents that modulate may be able alleviate symptoms CHE.

Language: Английский

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The circuit mechanisms of working memory: Key roles of the dorsolateral prefrontal cortex

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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