Neuroimmune Mechanisms In Chronic Inflammation

The nervous system plays an important role in the regulation of immunity and inflammation. On the other hand unbalanced immune responses in inflammatory and autoimmune conditions may have a deleterious impact on neuronal integrity and brain function. Recent studies have characterized neural pathways communicating peripheral inflammatory signals to the CNS, and brain- and spinal cord-derived circuitries controlling various innate and adaptive immune responses and inflammation. A prototypical neural reflex circuit that regulates immunity and inflammation is the vagus nerve-based “inflammatory reflex”. Ongoing research has revealed cellular and molecular mechanisms underlying these neural circuits and indicated new therapeutic approaches in inflammatory and autoimmune disorders. Pharmacological and bioelectronic modulation of neural circuitry has been successfully explored in preclinical settings of sepsis, arthritis, inflammatory bowel disease, obesity-driven disorders, diabetes and other diseases. These studies paved the way to successful clinical trials with bioelectronic neuronal modulation in rheumatoid arthritis and inflammatory bowel disease. Dysregulated release of cytokines and other inflammatory molecules may have a severe impact on brain function. Brain inflammation (neuroinflammation), imbalances in brain neuronal integrity and neurotransmitter systems, and cognitive impairment are characteristic features of post-operative conditions, sepsis, liver diseases, diabetes and other disorders characterized by immune and metabolic dysregulation. Derangements in cytokine release also play a pivotal role in depression. Characteristic brain reactive antibodies in autoimmune conditions, including systemic lupus erythematosus and neuromyelitis optica, significantly contribute to brain pathology and cognitive impairment. These studies, and the simultaneous characterization of neuro-protective cytokines, identified new therapeutic approaches for treating neurological complications in inflammatory and autoimmune disorders. This Frontiers Research Topic is a forum for publishing research findings and methodological and conceptual advances at the intersection of immunology and neuroscience. We hope that presenting new insight into bi-directional neuro-immune communication in inflammation and autoimmunity will foster further collaborations and facilitate the development of new efficient therapeutic strategies.

For those of us involved in research on the neural mechanisms that relate tissue damage to pain. it is becoming more evident that the sensation of pain and suffering could be considered as part of a mechanism that involves not only sizeable areas in the brain but also simultaneous activations of the immune and the endocrine systems as well. A consensus is growing among specialists in the field that pain involves the sharing of molecular mechanisms between the nervous, immune and endocrine systems that can interact at peripheral and, ultimately, central levels. Furthermore, chronic pain could then be looked upon as a corollary of the imbalance in the cross talk between these systems, which could lead to new treatment strategies. The aim of this book is not to deal with acute pain that serves as an alarm signal, but to attempt to explain the molecular mechanisms of chronic pains considered as a multifactorial syndrome or disease.

Inflammation is important in many diseases, yet it is hard to find current information on the pertinent cellular and molecular mechanisms of inflammation. This book is a current and authoritative review of various aspects of inflammation in mammalian organisms. Basic principles, including regulation by cytokines, lipid mediators, reactive oxygen species and leukocyte recruitment are followed by chapters on integrative aspects of inflammation, such as neutrophil extracellular traps, sepsis and granulomatous inflammation. Contents: TNF Superfamily in Inflammation (Marisol Veny, Richard Virgen-Slane and Carl F Ware) Complement as a Mediator of Inflammation (B Paul Morgan) Lipids and Inflammation (Valerie B O'Donnell, Robert C Murphy and Garret A FitzGerald) Reactive Oxygen Species (Ulla G Knaus) Leukocyte Adhesion (Klaus Ley and Zhichao Fan) Neutrophil Extracellular Traps (Tobias A Fuchs, Abdul Hakkim and Constantin F Urban) Sepsis (Jamison J Grailer, Matthew J Delano and Peter A Ward) Granulomatous Inflammation (Marc Hilhorst, Gene Hunder, Jörg Goronzy and Cornelia Weyand) Readership: Graduate students, medical doctors/ practitioners, researchers, pathologists and nutritionists in medicine and healthcare. Keywords: Cytokines;IL-1;TNF;Lipid Mediators;Bradykinin and Neuropeptides;Leukocyte Adhesion;Angiogenesis;Degranulation;Antimicrobial Peptides;Neutrophil Extracellular Traps (NETs);Pharmacologic Modulation of Inflammation;Sepsis;Complement;Oxygen Radicals;Reperfusion Injury;Resolution of Inflammation;Atherosclerosis;Granulomatous Inflammation;Inflammatory Bowel DiseaseReview: Key Features: Up-to-date resource Comprehensive review of the various facets of inflammation

Chronic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, inflammatory bowel diseases, and others typically stimulate a systemic response of the entire body. This response has a uniform character in many diseases because common pathways are switched on. The uniform response regulates systemic energy and water provision. However, long-term application of this program leads to typical disease sequelae such as fatigue / depressive symptoms, sleep disturbances, anorexia, malnutrition, muscle wasting – cachexia, cachectic obesity, insulin resistance, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal axis, elevated sympathetic tone, hypertension, volume expansion, decreased parasympathetic tone, inflammation–related anemia, bone loss, hypercoagulability, circadian rhythms of symptoms, and disease exacerbation by stress . The Origin of Chronic Inflammatory Systemic Diseases and Their Sequelae demonstrates concepts of neuroendocrine immunology, energy and water regulation, and evolutionary medicine in order to show that the uniform response that regulates systemic energy and water provision, has been positively selected for acute physiological responses and short-lived disease states, but is a misguided program in chronic inflammatory diseases and aging. Offers a broad conceptual framework with a strong clinical link, written in an easy to grasp style and demonstrating the link to aging research Describes the important principles derived from basic immunology that are used to explain pathogenesis of chronic inflammatory systemic diseases with a focus on autoimmunity Defines the bioenergetics and energy regulation of the body explaining common response pathways typical for systemic inflammation Makes use of evolutionary medicine theory to demonstrate the uniformity of the systemic response Explains the appearance of typical disease sequelae on the basis of the three pillars: neuroendocrine immunology, energy regulation, and evolutionary medicine theory Contains color figures and tables that explain the field to newcomers

As lifespans increase, more people around the world find themselves victims of chronic pain. In spite of this, treatment options continue to be severely limited. Anti-inflammatory drugs can only do so much, while painkillers like opioids have led to crippling addictions and fatal overdoses. The subject of the book is the role of immune cells, including glial cells, and neuroimmune interactions in chronic pain. The book begins by examining the preclinical and clinical evidence supporting the involvement of non-neuronal cells in chronic pain. It discusses the interactions between non-neuronal cells and neurons in the regulation of chronic pain. It then presents the implications of these findings, including promising and emerging treatments such as specialized pro-resolving mediators (SPMs, such as resolvins and protectins), immune cell therapy, and complementary and alternative medicine, as well as neuromodulation and regenerative medicine, which may prove to be the turning point for hundreds of millions of patients world-wide who struggle to escape from the shadow of chronic pain. The book presents ground-breaking research that will alter current perspectives on chronic pain.

This book integrates discoveries from recent years to show the diversity of molecular mechanisms that contribute to memory consolidation, reconsolidation, extinction, and forgetting. It provides a special focus on the processes that govern functional and structural plasticity of dendritic spines. In nine chapters, new and important ideas related to learning and memory processes will be presented. Themes discussed include the role of AMPA receptors in memory, two signalling cascades involved in local spine remodelling and memory, the role of extracellular matrix proteins in memory, the regulation of gene expression and protein translation, and mechanisms of retrieval-induced memory modulation and forgetting. We believe that the study of these topics represents a great step toward understanding the complexity of the brain and the processes it governs.

Advances in itch research have elucidated differences between itch and pain but have also blurred the distinction between them. There is a long debate about how somatic sensations including touch, pain, itch, and temperature sensitivity are encoded by the nervous system. Research suggests that each sensory modality is processed along a fixed, direct-line communication system from the skin to the brain. Itch: Mechanisms and Treatment presents a timely update on all aspects of itch research and the clinical treatment of itch that accompanies many dermatological conditions including psoriasis, neuropathic itch, cutaneous t-cells lymphomas, and systemic diseases such as kidney and liver disease and cancer. Composed of contributions from distinguished researchers around the world, the book explores topics such as: Neuropathic itch Peripheral neuronal mechanism of itch The role of PAR-2 in neuroimmune communication and itch Mrgprs as itch receptors The role of interleukin-31 and oncostatin M in itch and neuroimmune communication Spinal coding of itch and pain Spinal microcircuits and the regulation of itch Examining new findings on cellular and molecular mechanisms, the book is a compendium of the most current research on itch, its prevalence in society, and the problems associated with treatment.

Despite numerous recent studies and exciting discoveries in the field, only limited treatment is available today for the victims of acute neurological injuries. Animal Models of Acute Neurological Injuries provides a standardized methodology manual designed to eliminate the inconsistent preparations and variability that currently jeopardizes advances in the field. Contributed by top experts and many original developers of the models, each chapter contains a step-by-step, proven procedure and visual aids covering the most commonly used animal models of neurological injury in order to highlight the practical applications of animal models rather than the theoretical issues. This intensive volume presents its readily reproducible protocols with great clarity and consistency to best aid neuroscientists and neurobiologists in laboratory testing and experimentation. Comprehensive and cutting-edge, Animal Models of Acute Neurological Injuries is an ideal guide for scientists and researchers who wish to pursue this vital course of study with the proficiency and precision that the field requires.