Genetic insights into the relationship between immune cell characteristics and ischemic stroke: A bidirectional Mendelian randomization study

European Journal of Neurology, Journal Year: 2024, Volume and Issue: 31(5)

Published: Feb. 7, 2024

Ischemic stroke, a major contributor to global disability and mortality, is underpinned by intricate pathophysiological mechanisms, notably neuroinflammation immune cell dynamics. Prior research has identified nuanced often paradoxical link between phenotypes ischemic stroke susceptibility. The aim of this study was elucidate the potential causal links median fluorescence intensity (MFI) morphological parameters (MP) 731 types risk.

Language: Английский

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Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 27, 2024

Abstract Background Traumatic brain injury (TBI) is a significant risk factor for Alzheimer’s disease (AD), and accumulating evidence supports role adaptive immune B T cells in both TBI AD pathogenesis. We previously identified cell major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive expansion after TBI. also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII acutely reduced + splenic was neuroprotective. The current study investigated chronic effects 5xFAD mouse model, with without Methods 12-week-old male wild type (WT) mice were administered either antagonist (CAP) or vehicle, once at 30 min sham lateral fluid percussion (FPI). Analyses included flow cytometric analysis dural meninges spleen, histopathological brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, assessment motor neurobehavioral function over ensuing 6 months. Results 9-month-old had significantly more compared age-matched WT mice. A one-time treatment CAP this population Importantly, improved some immune, histopathological, impairments six Although FPI did not further elevate meningeal cells, it negate ability reduce 3 months age exacerbated aspects pathology mice, including reducing hippocampal neurogenesis, increasing plaque deposition CA3, altering microgliosis, disrupting structure. ameliorated but all these effects.

Language: Английский

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Intruders or protectors – the multifaceted role of B cells in CNS disorders

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 10, 2024

B lymphocytes are immune cells studied predominantly in the context of peripheral humoral responses against pathogens. Evidence has been accumulating recent years on diversity immunomodulatory functions that undertake, with particular relevance for pathologies central nervous system (CNS). This review summarizes current knowledge cell populations, localization, infiltration mechanisms, and function CNS associated tissues. Acute chronic neurodegenerative examined order to explore complex, sometimes conflicting, effects can have each context, implications disease progression treatment outcomes. Additional factors such as aging modulate proportions subpopulations over time also discussed neuroinflammatory response susceptibility. A better understanding multifactorial role populations may ultimately lead innovative therapeutic strategies a variety neurological conditions.

Language: Английский

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B cells and the stressed brain: emerging evidence of neuroimmune interactions in the context of psychosocial stress and major depression

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: April 8, 2024

The immune system has emerged as a key regulator of central nervous (CNS) function in health and disease. Importantly, improved understanding contributions to mood disorders provided novel opportunities for the treatment debilitating stress-related mental conditions such major depressive disorder (MDD). Yet, impact to, involvement of, B lymphocytes response stress is not well-understood, leaving fundamental gap our knowledge underlying theory depression. Several emerging clinical preclinical findings highlight pronounced consequences cells MDD may indicate roles modulating mood. This review will describe foundational observations implicating cell-psychological interactions, discuss potential mechanisms by which brain context disorders, research tools that support investigation their neurobiological impacts, remaining questions. goal here this discussion illuminate both scope limitations current regarding role cells, stress, mood,

Language: Английский

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B cell treatment promotes a neuroprotective microenvironment after traumatic brain injury through reciprocal immunomodulation with infiltrating peripheral myeloid cells

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: May 31, 2023

Traumatic brain injury (TBI) remains a major cause of death and severe disability worldwide. We found previously that treatment with exogenous naïve B cells was associated structural functional neuroprotection after TBI. Here, we used mouse model unilateral controlled cortical contusion TBI to investigate cellular mechanisms immunomodulation intraparenchymal delivery mature lymphocytes at the time injury. Exogenous showed complex time-dependent response in microenvironment, including significantly increased expression IL-10, IL-35, TGFβ, but also IL-2, IL-6, TNFα. After 10 days situ, cell subsets expressing IL-10 or TGFβ dominated. Immune infiltration into predominantly comprised myeloid cells, did not alter overall numbers infiltrating cells. In presence more produced fewer TNFα, interferon-γ IL-6 as compared controls, up 2 months post-TBI. proportion CD206+ monocytes/macrophages reduced relative activated microglia starting 4 post-injury. Ablation peripheral monocytes clodronate liposomes are required for inducing regulatory phenotype Reciprocally, specifically inflammatory cytokines Ly6C+ monocytes/macrophages. These data support hypothesis particularly monocyte/macrophages, key mediators neuroprotective immunomodulatory effects observed treatment.

Language: Английский

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Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

ABSTRACT Background The involvement of immune cells in the pathophysiology intracerebral hemorrhage (ICH) is becoming increasingly recognized, yet their specific causal contributions remain uncertain. objective this research to uncover potential interactions between diverse and ICH using Mendelian randomization (MR) analysis. Methods Genetic variants associated with 731 cell traits were sourced from a comprehensive genome‐wide association study (GWAS) involving 3757 participants. Summary statistics data for acquired FinnGen, comprising 4056 cases 371,717 controls. principal analytical tool utilized our was inverse‐variance weighted (IVW) method, incorporated as key component two‐sample MR approach. To mitigate biases verify stability conclusions drawn primary methods, series sensitivity analyses performed. Results analysis elucidated 33 associations, B (eight traits), conventional dendritic (cDC, two maturation stages T (two monocytes myeloid (five TBNK (six regulatory (Treg, eight traits). DP (CD4+CD8+) %T (OR = 0.83, CI 0.72–0.96, p 0.013) exhibited strongest protective effect. In contrast, transitional AC 1.09, 1.02–1.16, 0.006) IgD− CD27− %lymphocyte 1.08, 1.00–1.17, 0.045) showed higher tendency increase risk. validated robustness consistency these results. Conclusion Our provides robust evidence substantiating relationship immunophenotypes identification findings significantly enhances understanding pathogenic mechanisms underlying ICH, particularly pertaining system. This breakthrough paves way innovative clinical pharmaceutical opportunities, potentially promoting development targeted therapies enhanced strategies managing preventing ICH.

Language: Английский

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Comprehensive analysis of copper metabolism-related genes in immune infiltration in spinal cord injury (Preprint)

Published: Jan. 8, 2025

Spinal cord injury (SCI) is a complex chronic disease which can be classified into traumatic and non-traumatic. Copper metabolism forms programmed cell death autophagy in various diseases. To date, no studies on the mechanisms by copper metabolism-related genes regulate immune infiltration SCI have been reported. develop potential to assess of spinal injury. SCI-related microarray datasets were retrieved from Integrated gene Expression Database (GEO) standardized. Then quantitative was performed extracted through screened expression matrix. The difference between group normal correlation cells its function analyzed. most immune-related DEGs out construct risk model. Gene Ontology (GO) function, Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses drug target using Enrichr website database. Set Variation Analysis (GSVA) used analyze differences biological functions among different types. qRT-PCR investigate changes above 27 obtained merging GSE151371 datasets. Correlation analysis showed that BAX, CYCS, GSDMD, UCHL5, CASP9, MAP2K1 MAPK14 significantly correlated with cells. Subsequently, these seven included study, prediction model constructed calculate total score probability group. KEGG mainly enriched Hepatitis B, Kaposi sarcoma-associated herpesvirus infection, Human immunodeficiency virus 1 infection. 302 miRNAs predicted upstream DEGs. GSVA regulation pathways upregulated subgroup high . results vivo experiment changed after (P < 0.05). help evaluate infiltration, providing new direction for treatment SCI.

Language: Английский

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Advances in the Study of Small Cell Lung Cancer and Metabolic Syndrome

Asian Case Reports in Emergency Medicine, Journal Year: 2025, Volume and Issue: 13(02), P. 125 - 132

Published: Jan. 1, 2025

Language: Английский

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Spinal cord tethering and syringomyelia after trauma: impact of age and surgical outcome

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: July 15, 2023

Posttraumatic spinal cord tethering and syringomyelia frequently lead to progressive neurological loss. Although several studies demonstrated favourable outcome following detethering with/without shunting, additional research is required as no clear consensus exists over the ideal treatment strategy knowledge about prognostic demographic determinants currently limited. In this investigation, we retrospectively investigated 67 patients (56 men, 11 women) who were surgically treated followed for symptomatic from 2012 2022 at our center. Age (B-coefficient 0.396) severity of trauma - 0.462) have been identified independent predictors rate development (p < 0.001). Following untethering surgery including expansion duraplasty 65.9% an improvement loss 0.001) whereas 50.0% displayed amelioration spasticity and/or neuropathic pain Conclusively, active screening syringomyelia, particularly in younger with severe trauma, crucial surgical shunting able achieve clinical outcomes. This may enable clinicians tailor strategies injury suffering towards a more optimal personalized patient care.

Language: Английский

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Genetically supported causality between gut microbiota, immune cells, and ischemic stroke: a two-sample Mendelian randomization study

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: June 4, 2024

Background Previous studies have highlighted a robust correlation between gut microbiota/immune cells and ischemic stroke (IS). However, the precise nature of their causal relationship remains uncertain. To address this gap, our study aims to meticulously investigate association likelihood developing IS, employing two-sample Mendelian randomization (MR) analysis. Methods Our comprehensive analysis utilized summary statistics from genome-wide (GWAS) on microbiota, immune cells, IS. The primary MR method employed was inverse variance-weighted (IVW) approach. potential pleiotropy identify outlier genetic variants, we incorporated residual sum (MR-PRESSO) technique, along with MR-Egger regression. Heterogeneity assessed using Cochran’s Q-test. Additionally, leave-one-out conducted pinpoint any individual variant influencing observed associations. Finally, reverse performed explore causation. Results investigation revealed four microbial taxa 16 significant IS ( p &lt; 0.05). Notably, two bacterial features five immunophenotypes were strongly associated lower risk: genus. Barnesiella.id.944 (OR: 0.907, 95% CI: 0.836–0.983, = 0.018), LachnospiraceaeNK4A136group.id.11319 0.918, 0.853–0.983, 0.988), Activated &amp; resting Treg % CD4++ 0.977, 0.956–0.998, 0.028). associations risk eleven observed: Paraprevotella.id.962 1.106, 1.043–1.172, 0.001), Streptococcus.id.1853 1.119, 1.034–1.210, 0.005), CD127 granulocyte 1.039, 1.009–1.070, 0.011). analyses did not reveal heterogeneity based Cochrane’s Q-test &gt; 0.05) nor indicate instances horizontal according MR-PRESSO Furthermore, robustness results confirmed through Conclusion provides further evidence supporting microbiota in relation shedding light underlying mechanisms that may contribute condition. These findings lay solid foundation for future investigations into targeted prevention strategies.

Language: Английский

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