Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

Ischemic stroke is still among the leading causes of mortality and morbidity worldwide. Despite intensive advancements in medical sciences, the clinical options to treat ischemic stroke are limited to thrombectomy and thrombolysis using tissue plasminogen activator within a narrow time window after stroke. Current state of the art knowledge reveals the critical role of local and systemic inflammation after stroke that can be triggered by interactions taking place at the brain and immune system interface. Here, we discuss different cellular and molecular mechanisms through which brain–immune interactions can take place. Moreover, we discuss the evidence how the brain influence immune system through the release of brain derived antigens, damage-associated molecular patterns (DAMPs), cytokines, chemokines, upregulated adhesion molecules, through infiltration, activation and polarization of immune cells in the CNS. Furthermore, the emerging concept of stemness-induced cellular immunity in the context of neurodevelopment and brain disease, focusing on ischemic implications, is discussed. Finally, we discuss current evidence on brain–immune system interaction through the autonomic nervous system after ischemic stroke. All of these mechanisms represent potential pharmacological targets and promising future research directions for clinically relevant discoveries.

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The Yin and Yang of Innate Immunity in Stroke

BioMed Research International ◽

10.1155/2014/807978 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Xiaomeng Xu ◽

Yongjun Jiang

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Ischemic Stroke ◽

Immune System ◽

Innate Immune Response ◽

Time Window ◽

Adaptive Immune System ◽

Innate Immune ◽

Yin And Yang ◽

Molecular Patterns

Immune system plays an elementary role in the pathophysiological progress of ischemic stroke. It consists of innate and adaptive immune system. Activated within minutes after ischemic onset, innate immunity is responsible for the elimination of necrotic cells and tissue repair, while it is critically involved in the initiation and amplification of poststroke inflammation that amplifies ischemic damage to the brain tissue. Innate immune response requires days to be fully developed, providing a considerable time window for therapeutic intervention, suggesting prospect of novel immunomodulatory therapies against poststroke inflammation-induced brain injury. However, obstacles still exist and a comprehensive understanding of ischemic stroke and innate immune reaction is essential. In this review, we highlighted the current experimental and clinical data depicting the innate immune response following ischemic stroke, mainly focusing on the recognition of damage-associated molecular patterns, activation and recruitment of innate immune cells, and involvement of various cytokines. In addition, clinical trials targeting innate immunity were also documented regardless of the outcome, stressing the requirements for further investigation.

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Involvement of Probiotics and Postbiotics in the Immune System Modulation

Biologics ◽

10.3390/biologics1020006 ◽

2021 ◽

Vol 1 (2) ◽

pp. 89-110

Author(s):

Neslihan Yeşilyurt ◽

Birsen Yılmaz ◽

Duygu Ağagündüz ◽

Raffaele Capasso

Keyword(s):

Immune System ◽

Pharmaceutical Industry ◽

Intestinal Microbiota ◽

Health Benefits ◽

The Body ◽

Future Research ◽

Immune Systems ◽

Advantages And Disadvantages ◽

Immune System Modulation ◽

Molecular Patterns

Intestinal microbiota interacts with other systems, especially the immune system, which is responsible for protecting the body by recognizing “stranger” (pathogen associated molecular patterns-PAMPs) and “danger” (damage-associated molecular patterns-DAMPs) molecular motifs. In this manner, it plays an important role in the pathogenesis of various diseases and health. Despite the use of probiotics that modulate the intestinal microbiota in providing health benefits and in the treatment of diseases, there are some possible concerns about the possibility of developing adverse effects, especially in people with suppressed immune systems. Since probiotics provide health benefits with bioactive compounds, studies are carried out on the use of products containing non-living probiotic microorganisms (paraprobiotics) and/or their metabolites (postbiotics) instead of probiotic products. It is even reported that these microbial compounds have more immunomodulatory activities than living microorganisms via some possible mechanism and eliminates some disadvantages of probiotics. Considering the increasing use of functional foods in health and disease, further studies are needed with respect to the benefits and advantages of parabiotic and/or postbiotic use in the food and pharmaceutical industry as well as immune system modulation. Although probiotics have been extensive studied for a long time, it seems that postbiotics are promising tools for future research and applications according to the recent literature. This review aimed to evaluate the interaction of probiotics and postbiotics with the immune systems and also their advantages and disadvantages in the area of food-pharmaceutical industry and immune system modulation.

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Involvement of Microglia in the Pathophysiology of Intracranial Aneurysms and Vascular Malformations—A Short Overview

International Journal of Molecular Sciences ◽

10.3390/ijms22116141 ◽

2021 ◽

Vol 22 (11) ◽

pp. 6141

Author(s):

Teodora Larisa Timis ◽

Ioan Alexandru Florian ◽

Sergiu Susman ◽

Ioan Stefan Florian

Keyword(s):

Immune Cells ◽

Arteriovenous Malformations ◽

Intracranial Aneurysms ◽

Immune Cell ◽

Vascular Malformations ◽

Cerebral Injury ◽

Future Research ◽

Mortality And Morbidity ◽

The Central Nervous System ◽

The Brain

Aneurysms and vascular malformations of the brain represent an important source of intracranial hemorrhage and subsequent mortality and morbidity. We are only beginning to discern the involvement of microglia, the resident immune cell of the central nervous system, in these pathologies and their outcomes. Recent evidence suggests that activated proinflammatory microglia are implicated in the expansion of brain injury following subarachnoid hemorrhage (SAH) in both the acute and chronic phases, being also a main actor in vasospasm, considerably the most severe complication of SAH. On the other hand, anti-inflammatory microglia may be involved in the resolution of cerebral injury and hemorrhage. These immune cells have also been observed in high numbers in brain arteriovenous malformations (bAVM) and cerebral cavernomas (CCM), although their roles in these lesions are currently incompletely ascertained. The following review aims to shed a light on the most significant findings related to microglia and their roles in intracranial aneurysms and vascular malformations, as well as possibly establish the course for future research.

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Role of Immunity in Pathogenesis of Psychosis

10.5772/intechopen.98447 ◽

2021 ◽

Author(s):

Wafa Abdelghaffar ◽

Oussama Sidhom ◽

Lilia Laadhar ◽

Rym Rafrafi

Keyword(s):

Mental Health ◽

Immune System ◽

Psychiatric Symptoms ◽

Scientific Evidence ◽

Health Conditions ◽

Future Research ◽

Antineuronal Antibodies ◽

System Components ◽

The Brain

The involvement of immunity in the pathogenesis of schizophrenia and related psychoses was suspected a century ago but was shadowed by the dopaminergic hypothesis after the discovery of antipsychotics. We currently know that this latter theory has many limits and cannot account for the wide variety of psychotic conditions. The immune-inflammatory theory is now one of the most promising axes of research in terms of pathogenesis of several mental health conditions. Immunity and inflammation play a role at least in a subgroup of patients with psychosis. The immune system is complex with a variety of components and mediators that can all have effects on the brain and thus mediate psychiatric symptoms. In this chapter we will explore the scientific evidence of the role of immune system in pathophysiology of psychosis. The sections of this chapter will discuss the role of innate system components (cytokines, microglia, inflammation.), the role of adaptive system (lymphocytes and antibodies) with a section focusing on auto-immunity and particularly antineuronal antibodies. Finally we will discuss how this research can impact patients management and elaborate recommendations for future research.

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Gut Microbiome and Its Interaction with Immune System in Spondyloarthritis

Microorganisms ◽

10.3390/microorganisms8111727 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1727

Author(s):

Jacqueline So ◽

Lai-Shan Tam

Keyword(s):

Immune System ◽

Gut Microbiome ◽

Current Evidence ◽

Future Research ◽

Hla B27 ◽

Human Immune System ◽

Gut Inflammation ◽

Germ Free ◽

Gut Microorganisms

Emerging evidence suggests there is a gut-joint axis in spondyloarthritis (SpA). In a study, subclinical gut inflammation occurred in nearly 50% of SpA. Chronic gut inflammation also correlated with disease activity in SpA. Trillions of microorganisms reside in the human gut and interact with the human immune system. Dysbiosis affects gut immune homeostasis and triggers different autoimmune diseases including SpA. The absence of arthritis in HLA-B27 germ-free mice and the development of arthritis after the introduction of commensal bacteria to HLA-B27 germ-free mice proved to be the important role of gut bacteria in shaping SpA, other than the genetic factor. The recent advance in gene sequencing technology promotes the identification of microorganisms. In this review, we highlighted current evidence supporting the link between gut and axial SpA (axSpA). We also summarized available findings of gut microbiota and its interaction with the immune system in axSpA. Future research may explore the way to modulate gut microorganisms in axSpA and bring gut microbiome discoveries towards application.

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Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00207.2012 ◽

2013 ◽

Vol 305 (8) ◽

pp. G529-G541 ◽

Cited By ~ 65

Author(s):

Yehuda Ringel ◽

Nitsan Maharshak

Keyword(s):

Irritable Bowel Syndrome ◽

Immune Function ◽

Intestinal Microbiota ◽

Clinical Symptoms ◽

Current Evidence ◽

Future Research ◽

Gastrointestinal Microbiota ◽

Plausible Model ◽

Irritable Bowel ◽

The Brain

The pathophysiology of irritable bowel syndrome (IBS) is believed to involve alterations in the brain-gut axis; however, the etiological triggers and mechanisms by which these changes lead to symptoms of IBS remain poorly understood. Although IBS is often considered a condition without an identified “organic” etiology, emerging evidence suggests that alterations in the gastrointestinal microbiota and altered immune function may play a role in the pathogenesis of the disorder. These recent data suggest a plausible model in which changes in the intestinal microbiota and activation of the enteric immune system may impinge upon the brain-gut axis, causing the alterations in gastrointestinal function and the clinical symptoms observed in patients with IBS. This review summarizes the current evidence for altered intestinal microbiota and immune function in IBS. It discusses the potential etiological role of these factors, suggests an updated conceptual model for the pathogenesis of the disorder, and identifies areas for future research.

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PPARγExpression and Function in Mycobacterial Infection: Roles in Lipid Metabolism, Immunity, and Bacterial Killing

PPAR Research ◽

10.1155/2012/383829 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 52

Author(s):

Patricia E. Almeida ◽

Alan Brito Carneiro ◽

Adriana R. Silva ◽

Patricia T. Bozza

Keyword(s):

Molecular Mechanisms ◽

Critical Role ◽

Mycobacterial Infection ◽

Receptor Activation ◽

Host Cells ◽

Current Evidence ◽

Peroxisome Proliferator ◽

Bacterial Killing ◽

Peroxisome Proliferator Activated Receptor ◽

And Function

Tuberculosis continues to be a global health threat, with drug resistance and HIV coinfection presenting challenges for its control.Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a highly adapted pathogen that has evolved different strategies to subvert the immune and metabolic responses of host cells. Although the significance of peroxisome proliferator-activated receptor gamma (PPARγ) activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPARγduring mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPARγexpression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPARγexpression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPARγexpression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPARγexpression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPARγenhances mycobacterial killing capacity of macrophages, suggesting a role of PPARγin favoring the establishment of chronic infection. Collectively, PPARγis emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies.

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Catestatin (Cst) protects the brain against ischemia/reperfusion injury through suppressing ER-stress and mitochondrial dysfunction

10.21203/rs.3.rs-58676/v1 ◽

2020 ◽

Author(s):

Pei Bing ◽

Chunjie Song ◽

Zhengjiang Zhang ◽

Shen Xin ◽

Cui Qian

Keyword(s):

Ischemic Stroke ◽

Er Stress ◽

Mitochondrial Dysfunction ◽

Reperfusion Injury ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Protective Function ◽

The Brain

Abstract BackgroundCerebral stroke, known as a cerebral vascular accident (CVA), is one of the leading causes of long-term disability and the second leading cause of death worldwide. Despite amounts of advances that have been achieved in terms of the treatment of ischemic stroke. But thus far, clinically effective neuroprotectants remain elusive, which may mainly due to the lack of a complete understanding of molecular mechanisms of the stroke. Previous studies have been revealed that catestatin (Cst) is closely related to cardiovascular ischemia/reperfusion injuries. However, little is known about whether Cst is involved in the regulation of neuronal death processes during ischemia. MethodsIn the present study, we revealed a protective function of Cst on Rat neuron cell death in the setting of ischemia/reperfusion injury. ResultsWe found that Cst treatment significantly attenuated the deficits of hippocampal related behaviors. On mechanism, our data revealed that Cst administration remarkably reduced ER-stress and mitochondrial dysfunction caused by I/R injury, and subsequently protected brain cells from apoptosis. ConclusionIn sum, our results demonstrate that Cst ameliorates I/R injury-induced hippocampal-related behaviors deficits by protecting the neurons from I/R injury-induced ER-stress and mitochondrial dysfunction and apoptosis. Our findings may provide a promising novel neuroprotectant for ischemic stroke therapy.

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Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.620984 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yufei Xie ◽

Annemarie H. Meijer ◽

Marcel J. M. Schaaf

Keyword(s):

Immune System ◽

Inflammatory Response ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Critical Role ◽

Model Systems ◽

Trinitrobenzene Sulfonic Acid ◽

Inflammatory Drugs ◽

Anti Inflammatory

Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses in vivo at the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.

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LARGE-SCALE GENOME SAMPLING REVEALS UNIQUE IMMUNITY AND METABOLIC ADAPTATIONS IN BATS

10.22541/au.160977727.76870866/v1 ◽

2021 ◽

Author(s):

Diana Moreno Santillan ◽

Tanya Lama ◽

Yocelyn Gutiérrez Guerrero ◽

Alexis Brown ◽

Paul Donat ◽

...

Keyword(s):

Immune System ◽

Gene Family ◽

Molecular Mechanisms ◽

Small Body ◽

Gene Family Evolution ◽

Comparative Genomic ◽

Metabolic Genes ◽

Pathway Gene ◽

Genomic Study ◽

Molecular Patterns

Comprising more than 1400 species, bats possess adaptations unique among mammals including powered flight, unexpected longevity given small body size, and extraordinary immunity. Some of the molecular mechanisms underlying these unique adaptations includes DNA repair, metabolism and immunity. However, analyses have been limited to a few divergent lineages, reducing the scope of inferences on gene family evolution across the Order Chiroptera. We conducted an exhaustive comparative genomic study of 37 bat species encompassing a large number of lineages, with a particular emphasis on multi-gene family evolution across immune system and metabolic genes. In agreement with previous analyses, we found lineage-specific expansions of the APOBEC3 and MHC-I gene families, and loss of the proinflammatory PYHIN gene family. We inferred more than 1,000 gene losses unique to bats, including genes involved in the regulation of inflammasome pathways such as epithelial defense receptors, the natural killer gene complex and the interferon-gamma induced pathway. Gene set enrichment analyses revealed genes lost in bats are involved in defense response against pathogen-associated molecular patterns and damage-associated molecular patterns. Gene family evolution and selection analyses indicate bats have evolved fundamental functional differences compared to other mammals in both innate and adaptive immune system, with the potential to enhance anti-viral immune response while dampening inflammatory signaling. In addition, metabolic genes have experienced repeated expansions related to convergent shifts to plant-based diets. Our analyses support the hypothesis that, in tandem with flight, ancestral bats had evolved a unique set of immune adaptations whose functional implications remain to be explored.

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