This PIR volume presents a comprehensive collection of reviews that focus on the role of the blood-brain barrier (BBB) during steady-state and inflamed conditions. Within the central nervous system (CNS) the constantly changing bloodstream is strictly separated from the CNS parenchyma by the BBB. However, viruses, bacteria, parasites and auto-aggressive immune cells can penetrate the barrier and significantly contribute to CNS inflammation. The BBB can actively contribute to neuroinflammation by presentation of chemokines, expression of cell adhesion molecules and alterations of barrier properties. As such, understanding the role of the BBB under healthy and pathological conditions is essential to the development of new drugs to efficiently combat inflammatory diseases of the CNS.

This volume contains the most recent works on intracranial pressure and neuromonitoring in brain injury selected from 300 abstracts submitted to the 10th International Symposium on Intracranial Pressure. It includes state of the art monitoring of the brain injured patient in intensive care as well as the current state of knowledge in neurochemical and oxygen monitoring of the injured brain. Recent advances in molecular mechanisms of injury and the pathophysiology of ischemia and trauma are also included. "... this publication presents a comprehensive survey of the present state of art in the field and thus gives directions for further research to those engaged in ICP measurement and neuromonitoring”. Intensive Care Med

Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme

The microcirculation is highly responsive to, and a vital participant in, the inflammatory response. All segments of the microvasculature (arterioles, capillaries, and venules) exhibit characteristic phenotypic changes during inflammation that appear to be directed toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. The best characterized responses of the microcirculation to inflammation include impaired vasomotor function, reduced capillary perfusion, adhesion of leukocytes and platelets, activation of the coagulation cascade, and enhanced thrombosis, increased vascular permeability, and an increase in the rate of proliferation of blood and lymphatic vessels. A variety of cells that normally circulate in blood (leukocytes, platelets) or reside within the vessel wall (endothelial cells, pericytes) or in the perivascular space (mast cells, macrophages) are activated in response to inflammation. The activation products and chemical mediators released from these cells act through different well-characterized signaling pathways to induce the phenotypic changes in microvessel function that accompany inflammation. Drugs that target a specific microvascular response to inflammation, such as leukocyte-endothelial cell adhesion or angiogenesis, have shown promise in both the preclinical and clinical studies of inflammatory disease. Future research efforts in this area will likely identify new avenues for therapeutic intervention in inflammation. Table of Contents: Introduction / Historical Perspectives / Anatomical Considerations / Impaired Vasomotor Responses / Capillary Perfusion / Angiogenesis / Leukocyte-Endothelial Cell Adhesion / Platelet-Vessel Wall Interactions / Coagulation and Thrombosis / Endothelial Barrier Dysfunction / Epilogue / References

This book provides comprehensive information, both for clinicians and scientists, on the basic mechanisms, clinical features, and therapeutic approaches to epilepsy as an inflammatory disease. Inflammation has been for many years considered as an etiologic player (and a therapeutic target) for a specific group of epilepsies. However, it turns out that this concept underestimated the impact of inflammation in seizure disorders. Many accepted therapies for non-inflammatory epilepsies act in part as an inflammatory drug. The CNS actively responds to acute immune challenges by altering body temperature, stimulating the HPA axis, as well as up- and down-regulating specific sympathetic pathways.

In this book the recent advancements in understanding the gut-brain interaction as well as gut microbiome and how this interaction plays a vital role in human health and disease are discussed. Each chapter gives an analysis of questions, research directions, and methods within the field of gut-brain axis. The readers will benefit from the latest knowledge about our understanding about how gut-brain axis and modulation of gut microbiome determines predisposition to neurological disorders. The multidisciplinary book is essential reading for anyone interested in the field of gut-brain axis and gut microbiome: from undergraduates to graduate students as well as scientists and physicians having an interest in the new exciting field of gut microbiome and its relationship with brain function.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

Pituitary Adenylate Cyclase-Activating Polypeptide is the first volume to be written on the neuropeptide PACAP. It covers all domains of PACAP from molecular and cellular aspects to physiological activities and promises for new therapeutic strategies. Pituitary Adenylate Cyclase-Activating Polypeptide is the twentieth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.

For many years, the immune and central nervous systems were thought to function independently with little or no interaction between the two. This view has und- gone dramatic changes over the past three decades. Indeed, we now know that there exists various feedback loops between the brain and immune systems that impact signi cantly upon different behavioral processes, including normal behavior and mental disorders. Pioneering efforts in generating this change were initiated by a number of early investigators. Included were those whose efforts were directed at establishing neuroimmune connections as well as others whose research focused upon the relationship between immunity, cytokines, and behavior. This book brings together outstanding scientists and clinicians who have made major contributions to the rapidly developing eld investigating the relationship between immunity and behavior. The book is divided into three parts. The rst part describes pathways by which the brain and immune systems communicate and int- act with each other. In the chapter “Cytokines and the Blood–Brain Barrier” p- vides insight into interactions between the blood–brain barrier and cytokines. Such interactions underlie basic communication between the immune system and brain that are present in normal as well as in disease conditions. In the chapter “Neu- chemical and Endocrine Responses to Immune Activation: The Role of Cytokines,” the neurochemical and endocrine consequences of immune challenge and cytokine administration on central neurotransmitter activity are discussed.

‘Connectivity and Functional Specialization in the Brain’ is a topic that describes nerve cells in terms of their anatomical and functional connections. The term connectome refers to a comprehensive map of neural connections, like a wiring diagram of an organism’s nervous system. Connectomics, the study of connectomes, can be applied to individual neurons and their synaptic connections, as well as to connections between neuronal populations or to functional and structural connectivity of different brain regions. This book addresses neural connectivity at these various scales in health and disease. The chapters review novel findings related to neuroanatomy and cell biology, neurophysiology, neural plasticity, changes of connectivity in neurological disorders, and sensory system connectivity. The book provides the reader with an overview of the current state-of-the-art of research of neural connectivity and focuses on the most important evidence-based developments in this area. Individual chapters focus on recent advances in specific areas of neural connectivity and in different brain regions. All chapters represent recent contributions to the rapidly developing field of neural connectivity.