The Blood Brain Barrier and Inflammation

Author: Ruth Lyck
Publisher: Springer
ISBN: 3319455141
Format: PDF, ePub, Docs
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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.

Inflammatory Signalling at the Blood brain Barrier

Author: Leon Smyth
Publisher:
ISBN:
Format: PDF, ePub
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The blood-brain barrier (BBB) is an important protective structure that restricts the free passage of blood components and circulating immune cells into the brain. The BBB is primarily composed of endothelial cells that line the inside of the vessel, and is surrounded by pericytes that perform critical roles in its formation and maintenance. In this project, I aimed to examine aspects of inflammatory signalling at the BBB using primary human brain pericytes and endothelia. Initially, pericytes were characterised in human brain tissue to develop a panel of markers for pericytes in vitro. Characterisation studies validated that in vitro cultures of pericytes recapitulated their in situ phenotype, as well as identifying two novel markers of vascular smooth muscle cell phenotype in situ and in vitro. A protocol for the isolation of primary human brain endothelia was then developed to study the interactions of pericytes and endothelia in vitro, and these cultures were shown to retain their unique brain endothelial phenotype. Using cultures of pericytes and endothelia, differences in the inflammatory response of these two cell types were identified, including unique secretions, and differential sensitivity to inflammatory stimuli. Subsequently, the role of platelet-derived growth factor-BB (PDGF-BB) was investigated in greater detail. PDGF-BB was found to cause a proliferative response in brain pericytes, as has been found previously, but also induced the expression of inflammation-related secretions. The pathways through which this inflammatory response was mediated were dissected using genetic and pharmacological inhibitors. Interestingly, it was found that PDGF-BB altered pericyteendothelial interactions, stopping pericytes from strengthening the endothelial barrier. The role of PDGF-BB was investigated further in co-cultures, incorporating astrocytes, microglia, endothelia, and pericytes. It was observed that PDGF-BB improves the formation of blood vessel-like endothelial cords in vitro due to reduced cell death and increased expression of angiogenesis-associated molecules, reminiscent of its effects in vivo. The BBB is a critical structure in the brain, but has not yet been targeted to treat disease. Together these findings provide novel insights into cell-cell signalling at the BBB, and how these interactions are modified during inflammatory conditions. Because BBB damage and neuroinflammation are critical disease processes in neurological diseases, the factors that govern neuroinflammation at the BBB present potential drug targets to prevent the progression of AD.

Systemic Inflammation and Blood brain Barrier Abnormality in Relapsing remitting Multiple Sclerosis

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ISBN:
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Abstract: Background: Systemic inflammation can affect disease expression in multiple sclerosis. The mechanism might involve blood–brain barrier disruption. We aimed to assess the effects of systemic inflammation on disease progression in multiple sclerosis and the role of blood–brain barrier disruption. Methods: We recruited adults with relapsing–remitting multiple sclerosis and healthy controls from the general population. Three-dimensional dynamic-contrast enhanced MRI was used to measure blood–brain barrier permeability in the normal-appearing white matter (NAWM). Urinary neopterin, a product of activated macrophages, was measured to provide a readout of systemic inflammation. All study activities were performed in University Hospital Southampton after ethics approval (REC 12/SC/0176). Findings: 12 patients with mutliple sclerosis and 12 healthy controls were recruited. Blood–brain barrier permeability in NAWM, measured as the constant Ktrans, was significantly higher in patients than in controls (mean 0·024 ml/100g per min [SD·0·018] vs 0·006 [0·004], p=0·015). Systemic inflammatory activity, measured as the urinary neopterin:creatinine ratio (UNCR), was also significantly higher (3·35 [1·98] vs 1·36 [0·29], p=0·002). Across all participants, there was a weak positive correlation between Ktrans and UNCR ( r =0·40, p=0·031). Interpretation: Our findings support the hypothesis that the effects of systemic inflammation on expression of multiple sclerosis disease are mediated by blood–brain barrier disruption. Targeting this disruption and systemic inflammation might provide novel avenues for disease-modifying therapy. Funding: University of Southampton, National Institute for Health Research, Multiple Sclerosis Society.

The Brain and Host Defense

Author:
Publisher: Elsevier
ISBN: 9780444535450
Format: PDF, Kindle
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It is now well recognized that the brain, and especially the hypothalamus, plays an important role in the regulation of immune reactions and inflammation. This book aims to review our current state of knowledge of this important field. Key historical findings are presented, and the reciprocal interactions between the brain and the immune system are examined. Particular emphasis is placed on inflammation, a critical host defense reaction that serves as an effector response for both the adaptive and innate immune systems. Mechanisms implicated in brain defense, as well as in more general host defense, are discussed. The regulatory influences of the brain on inflammatory responses are included with particular reference to the role of the hypothalamus, which is also the main director the hormonal regulation of immune/inflammatory. Gender-related differences in immune responsiveness, circadian modulator of immune responses, and evidence that behavioral conditioning (e.g. reward) of immune responses is possible are used as examples to reinforce the notion that the neuroendocrine system exerts a fundamental and complex regulatory influence on the immune system. * Presents timely issues such as immunological aspects of the blood-brain-barrier and the role of inflammatory mediators in the evolution of strokes and degenerative diseases * Includes analysis of the role of the brain in the adaptive responses to disease * Evaluates the argument that further knowledge of the influence of the brain on the immune system will provide new insights to the pathophysiology infectious and autoimmune diseases

Gesammelte Arbeiten zur Immunit tsforschung Classic Reprint

Author: Paul Ehrlich
Publisher: Forgotten Books
ISBN: 9781332635948
Format: PDF, ePub, Mobi
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Excerpt from Gesammelte Arbeiten zur Immunitätsforschung Der jüngste Congress fur Hygieneund Demographie in Brussel, auf dem die wichtigsten Fragen der Immunitätslehre zur Discussion standen, hat gezeigt, wie es auch nicht anders zu erwarten war, dass meine Theorie nicht von allen Forschern auf diesem Gebiet acceptirt ist, sondern dass meine Anschauungen noch einzelne Gegner finden. Nichts kann ja einer wissenschaftlichen Frage mehr nutzen, als wenn Meinungsverschiedenheiten auftauchen, welche auf Grund experimenteller Forschungen zur kritischen Beleuchtung und zur weiteren Vertiefung des Gegenstandes führen, und so darf ich wohl sagen, dass es gerade die Gegnerschaft von Bord et und anderen hervorragenden Forschern des Instituts Pasteur gewesen ist, die mich und meine Mitarbeiter zu immer neuer experimen teller Arbeit und damit immer festerer Begründung meiner Theorie angespornt hat. Weniger erfreulich ist es dagegen, wenn Autoren wie Gruber, die in den Hauptfragen jeder eigenen Erfahrung ent behren, hauptsächlich auf Grund einiger literarischer Studien hin einen erbitterten Kampf führen, ohne dass sie in der Lage sind, sich in der Ueberfülle richtiger uud falscher Beobachtungen, welche die täglich anwachsende Literatur bringt, genügend zu orientiren, und wenn solche Gegner dann der Schwäche ihrer Argumente durch die heftige und persönliche Art ihres Angriffes aufzuhelfen suchen. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works.

The Blood Brain Barrier in Health and Disease Volume Two

Author: Katerina Dorovini-Zis
Publisher: CRC Press
ISBN: 1498727093
Format: PDF, ePub, Mobi
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Located at the interface between blood and the brain, the blood-brain barrier is a dynamic permeability barrier formed by a continuous layer of specialized endothelial cells endowed with important permeability, transport, and regulatory functions that both protect the internal milieu of the brain and allow essential nutrients to be transported into the brain. Abnormalities of the blood-brain barrier are increasingly recognized as a key component in the pathogenesis of a range of primary diseases of the brain and the secondary involvement of the brain from pathological processes in other organs. In The Blood-Brain Barrier in Health and Disease, Volume 2, international experts present comprehensive reviews and research accounts on blood-brain barrier dysfunction in infectious and inflammatory diseases, cerebrovascular diseases, stroke, trauma, vitamin deficiency, exposure to neurotoxicants, primary and metastatic brain tumors, and neurodegenerative diseases. This book is intended to serve as a guide and reference to basic and advanced information for researchers, students, and clinicians interested in this fast-expanding field and stimulate further research well into the future.

Biology and Physiology of the Blood Brain Barrier

Author: Pierre-Olivier Couraud
Publisher: Springer Science & Business Media
ISBN: 1475794894
Format: PDF
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The endothelial cells of the cerebral vasculature constitute, together with perivascular elements (astrocytes, pcricytes, basement membrane), the blood-brain barrier (BBB), which strictly limits and specifically controls the exchanges between the blood and the cerebral extracellular spacc.The existence of such a physical, enzymatic, and active barrier isolating the central nervous system has broad physiological, biological, pharmacological, and patho logical consequences, most of which are not yet fully elucidated. The Cerebral Vascular Biology conference (CVB '95) was organized and held at the "Carre des Sciences" in Paris on July I 0-12, 1995. Like the CVB '92 conference held in Duluth, Minnesota, three years ago, the objectives were to provide a forum for presentation of the most recent progresses and to stimulate discussions in the ticld of the biology, physiology. and pathology of the blood-brain barrier. The Paris conference gathered more than !50 participants. including investigators in basic neuroscience, physicians. and stu dents, who actively contributed to the scientific program by their oral or poster presentations. This volume contains a collection of short articles that summarize most of the new data that were presented at the conference. Six thematic parts focus on physiological transports. drug delivery, multidrug resistance P-glycoprotein, signal transduction at the BBB. interactions between the immune system and the cerebral endothelial cells, and the blood-brain barrier-related pathologies in the central nervous system. In addition, two introductory articles present new insights in the rapidly evolving topics of cerebral angiogenesis and gene transfer to the brain.

The Blood Brain Barrier BBB

Author: Gert Fricker
Publisher: Springer
ISBN: 3662437872
Format: PDF, ePub, Mobi
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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.

Animal Physiology Blood Brain Barrier Warm Blooded Inflammation Perspiration Reflex Physiology of Dinosaurs Thermoregulation

Author: Source Wikipedia
Publisher: Books LLC, Wiki Series
ISBN: 9781156392805
Format: PDF, ePub, Mobi
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Please note that the content of this book primarily consists of articles available from Wikipedia or other free sources online. Pages: 64. Chapters: Blood-brain barrier, Warm-blooded, Inflammation, Perspiration, Reflex, Physiology of dinosaurs, Thermoregulation, Insect physiology, Urine, Feces, Spermatogenesis, Lactation, Brochosome, Dog odor, Bone healing, Endotherm, Poikilotherm, Blood type, Preflexes, Cow dung, Bone remodeling period, Kleptothermy, Adaptation, Ossification, Desquamation, Ectotherm, Torpor, Heterothermy, Myogenic, Blood-testis barrier, Crenation, Foramen of Panizza, Thermal neutral zone, Gigantothermy, Homeotherm, Anticor, Tissue hydration, Peloids, Lymph Hearts, Amebocyte, Voluntary action, Bradymetabolism, Critical thermal maximum, Bulk endotherms, Dander. Excerpt: The physiology of dinosaurs has historically been a controversial subject, particularly thermoregulation. Recently, many new lines of evidence have been brought to bear on dinosaur physiology generally, including not only metabolic systems and thermoregulation, but on respiratory and cardiovascular systems as well. During the early years of dinosaur paleontology, it was widely considered that they were sluggish, cumbersome, and sprawling cold-blooded lizards. However, with the discovery of much more complete skeletons in the western United States, starting in the 1870s, scientists could make more informed interpretations of dinosaur biology and physiology. Edward Drinker Cope, opponent of Othniel Charles Marsh in the Bone Wars, propounded at least some dinosaurs as active and agile, as seen in the painting of two fighting "Laelaps" produced under his direction by Charles R. Knight. In parallel, the development of Darwinian evolution, and the discoveries of Archaeopteryx and Compsognathus, led Thomas Henry Huxley to propose that dinosaurs were closely related to birds. Despite these considerations, the image of dinosaurs as large reptiles had taken root, and most aspects of their p...