Proteins Involved in Synaptic Plasticity Are Downregulated in the Cerebrospinal Fluid of Infants With Clinical Sepsis Complicated by Neuroinflammation

Jiang, Pingping; Peng, Shan-Shan; Pankratova, Stanislava; Luo, Ping; Zhou, Ping; Chen, You

doi:10.3389/fncel.2022.887212

Cited by 7 publications

(5 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inflammation itself may be a trigger of adverse neurodevelopmental processes through epigenetic shared vulnerabilities (Jiang et al, 2022; Meszaros et al, 2012; Tylee et al, 2018). Immune-genetic processes may be more vulnerable to being triggered by an underlying inflammation or the fever itself (Garcia-Argibay et al, 2022; Ryan & Kastner, 2008).…”

Section: Discussionmentioning

confidence: 99%

The Association Between Repeated Measured Febrile Episodes During Early Childhood and Attention Deficit Hyperactivity Disorder: A Large-Scale Population-Based Study

Israel,

Merzon,

Krone

et al. 2024

J Atten Disord

View full text Add to dashboard Cite

Objective: We examined the association between the number, magnitude, and frequency of febrile episodes during the 0 to 4 years of life and subsequent diagnosis of ADHD. Methods: This population-based case-control study in an Israeli HMO, Leumit Health Services (LHS), uses a database for all LHS members aged 5 to 18 years between 1/1/2002 and 1/30/2022. The number and magnitude of measured fever episodes during the 0 to 4 years were recorded in individuals with ADHD ( N = 18,558) and individually matched non-ADHD controls in a 1:2 ratio ( N = 37,116). Results: A significant, independent association was found between the number and magnitude of febrile episodes during the 0 to 4 years and the probability of a later diagnosis of ADHD. Children who never had a measured temperature >37.5°C had a significantly lower rate of ADHD (OR = 0.834, 95% CI [0.802, 0.866], p < .0001). Conclusions: Febrile episodes during 0 to 4 years are associated with a significantly increased rate of a later diagnosis of ADHD in a doseresponse relationship.

show abstract

Section: Discussionmentioning

confidence: 99%

The Association Between Repeated Measured Febrile Episodes During Early Childhood and Attention Deficit Hyperactivity Disorder: A Large-Scale Population-Based Study

Israel,

Merzon,

Krone

et al. 2024

J Atten Disord

View full text Add to dashboard Cite

show abstract

“…Of course, during infarction or hemorrhage, CRP from the micro‐circulation is also in direct contact with inflamed tissue and creates hotspots of mCRP emanating from the core/origin (Figure 2 ; [ 35 ]).…”

Section: Monomeric Crp Dynamics Within the Brain And Effects Upon Blo...mentioning

confidence: 99%

Monomeric C‐reactive protein: A novel biomarker predicting neurodegenerative disease and vascular dysfunction

et al. 2023

View full text Add to dashboard Cite

Circulating C‐reactive protein (pCRP) concentrations rise dramatically during both acute (e.g., following stroke) or chronic infection and disease (e.g., autoimmune conditions such as lupus), providing complement fixation through C1q protein binding. It is now known, that on exposure to the membranes of activated immune cells (and microvesicles and platelets), or damaged/dysfunctional tissue, it undergoes lysophosphocholine (LPC)‐phospholipase‐C‐dependent dissociation to the monomeric form (mCRP), concomitantly becoming biologically active. We review histological, immunohistochemical, and morphological/topological studies of post‐mortem brain tissue from individuals with neuroinflammatory disease, showing that mCRP becomes stably distributed within the parenchyma, and resident in the arterial intima and lumen, being “released” from damaged, hemorrhagic vessels into the extracellular matrix. The possible de novo synthesis via neurons, endothelial cells, and glia is also considered. In vitro, in vivo, and human tissue co‐localization analyses have linked mCRP to neurovascular dysfunction, vascular activation resulting in increased permeability, and leakage, compromise of blood brain barrier function, buildup of toxic proteins including tau and beta amyloid (Aβ), association with and capacity to “manufacture” Aβ‐mCRP‐hybrid plaques, and, greater susceptibility to neurodegeneration and dementia. Recently, several studies linked chronic CRP/mCRP systemic expression in autoimmune disease with increased risk of dementia and the mechanisms through which this occurs are investigated here. The neurovascular unit mediates correct intramural periarterial drainage, evidence is provided here that suggests a critical impact of mCRP on neurovascular elements that could suggest its participation in the earliest stages of dysfunction and conclude that further investigation is warranted. We discuss future therapeutic options aimed at inhibiting the pCRP‐LPC mediated dissociation associated with brain pathology, for example, compound 1,6‐bis‐PC, injected intravenously, prevented mCRP deposition and associated damage, after temporary left anterior descending artery ligation and myocardial infarction in a rat model.

show abstract

“…Thus, factors that dysregulate the innate immune function of Aβ during infection may lead to downstream activation of potentially deleterious inflammation. While potential roles for Aβ in sepsis have been studied in animal models, there is a paucity of studies in humans [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Amyloid-β and caspase-1 are indicators of sepsis and organ injury

Tuckey,

Brandon,

Eslaamizaad

et al. 2023

ERJ Open Res

View full text Add to dashboard Cite

BackgroundSepsis is a life-threatening condition that results from a dysregulated host response to infection, leading to organ dysfunction. Despite the prevalence and associated socioeconomic costs, treatment of sepsis remains limited to antibiotics and supportive care, and a majority of intensive care unit (ICU) survivors develop long-term cognitive complications post- discharge. The present study identifies a novel regulatory relationship between amyloid-β (Aβ) and the inflammasome-caspase-1 axis as key innate immune mediators that define sepsis outcomes.MethodsMedical ICU patients and healthy individuals were consented for blood and clinical data collection. Plasma cytokine, caspase-1, and Aβ levels were measured. Data were compared against indices of multi-organ injury and other clinical parameters. Additionally, recombinant proteins were testedin vitroto examine the effect of caspase-1 on a functional hallmark of Aβ, namely aggregation.ResultsPlasma caspase-1 levels displayed the best predictive value in discriminating ICU patients with sepsis from non-infected ICU patients (AUROC=0.7080). Plasma caspase-1 and the 40 amino acid Aβ isoform (Aβx−40) showed a significant positive correlation and Aβx-40associated with organ injury. Additionally, Aβ plasma levels continued to rise from time of ICU admission to 7-days post-admission.In silico, Aβ harbors a predicted caspase-1 cleavage site, andin vitrostudies demonstrated that caspase-1 cleaved Aβ to inhibit its auto-aggregation, suggesting a novel regulatory relationship.ConclusionsAβx-40and caspase-1 are potentially useful early indicators of sepsis and its attendant organ injury. Additionally, Aβx-40has emerged as a potential culprit in the ensuing development of post-ICU-syndrome.

show abstract

Proteins Involved in Synaptic Plasticity Are Downregulated in the Cerebrospinal Fluid of Infants With Clinical Sepsis Complicated by Neuroinflammation

Cited by 7 publications

References 65 publications

The Association Between Repeated Measured Febrile Episodes During Early Childhood and Attention Deficit Hyperactivity Disorder: A Large-Scale Population-Based Study

The Association Between Repeated Measured Febrile Episodes During Early Childhood and Attention Deficit Hyperactivity Disorder: A Large-Scale Population-Based Study

Monomeric C‐reactive protein: A novel biomarker predicting neurodegenerative disease and vascular dysfunction

Amyloid-β and caspase-1 are indicators of sepsis and organ injury

Contact Info

Product

Resources

About