Download or read book Investigating the Role of Prostaglandin E2 Mediated Neuroinflammation in Models of Neurodegeneration written by Suraj Pradhan and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Parkinson's Disease (PD) pathophysiology is primarily characterized by the accumulation of misfolded protein aggregates of alpha-synuclein and degeneration of neurons throughout the CNS, in particular the dopaminergic (DA) neurons in the substantia nigra pars compacta. The mechanisms driving these processes, however, remain poorly understood. Recent studies have identified non cell-autonomous mechanisms such as inflammation and oxidative stress as major contributors to disease pathology in various neurodegenerative diseases including PD. Neurotoxicity in PD patients and animal models of PD is accompanied by significant increases in microgliosis and astrocytosis. Reactive microglia and astrocytes influence the local tissue environment by secreting inflammatory factors such as cytokines, chemokines, and reactive oxygen and nitrogen species. These inflammatory mediators have been suggested to promote the aggregation of alpha-synuclein in vitro and result in secondary neurotoxicity to DA neurons in vivo. Consistent with these observations, inhibiting inflammation is neuroprotective in animal models of Parkinsonism and may exert preventive effects in human PD. Previous data from our lab and others have shown that different prostaglandin E2 (PGE2) receptors amplify or dampen microglial inflammation in a disease setting. In this dissertation I investigated the contribution of PGE2 mediated inflammatory processes to neurodegeneration in mouse models of Parkinsonism. I focused on two receptors, the EP2 and EP4 receptor, which are expressed in neurons, astrocytes, and microglia. To probe the role of EP2 and EP4 in an inflammatory context, I stimulated microglia with oligomeric alpha-synuclein in vitro and injected mice with the neurotoxin MPTP in vivo. I used receptor agonists and antagonists to inhibit or activate the EP receptors and utilized the Cre-loxP genetic strategy to conditionally knock-out the receptors from specific cell types in the brain. My results show that PGE2 promotes neuroinflammation through the microglial EP2 receptor, and conversely suppresses it through the microglial EP4 receptor. Specifically, activating microglial EP2 increases the production of pro-inflammatory factors in vitro, and deleting microglial EP2 reduces MPTP associated microgliosis and astrocytosis in vivo. On the other hand, activating microglial EP4 suppresses the secretion of pro-inflammatory cytokines, chemokines, and ROS in vitro, and deleting microglial EP4 enhances MPTP associated microgliosis, astrocytosis, and infiltration of T-cells in vivo. Furthermore, systemically treating animals with an EP4 receptor agonist exerts a neuroprotective effect in the MPTP model. These results suggest that EP receptors may be potential therapeutic drug-targets for the treatment of PD and associated neurodegenerative diseases. My work shows that PGE2 is a critical inflammatory signaling molecule that plays a context-dependent and cell-specific role in neurodegeneration. My results support the hypothesis that the EP2 receptor plays a pro-inflammatory role while the EP4 receptor plays an anti-inflammatory and neuroprotective role in models of Parkinsonism. Understanding the contribution of PGE2 to the progression of Parkinsonian pathology has given us novel insights into the mechanisms of neuroinflammation and neurodegeneration.

Download or read book Involvement of Neuroinflammation in Models of Neurodegeneration written by Xiaochun Zhang and published by ProQuest. This book was released on 2008 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuroinflammation refers to the inflammatory process which occurs in the central nervous system. It consists of complex events including microglial activation, astrogliosis, and release of numerous inflammatory mediators. Neuroinflammation has been suspected to be involved in the pathologies of diverse neurodegenerative diseases. However, due to the multiple effects of its components, the role of neuroinflammation remains ambiguous. It is unclear whether the neuroinflammatory response is detrimental, beneficial or neutral. In this thesis, the involvement of neuroinflammation in different models of neurodegeneration was investigated with a focus on the methamphetamine (MA) induced dopaminergic terminal degeneration and an important inflammatory mediator -cyclooxygenase (COX). In the acute toxic dosing model of MA, our results show that COX-1 is unlikely to be involved in the MA-induced defects of the dopaminergic system. The COX-2 containing cells are targets of the damage during early stages of acute MA toxicity and selective inhibition of COX-2 enzyme is harmful rather than protective in this stage. The COX-2 induction appears 72 hours following acute MA administration which may be mediated by the activation of the nuclear transcription factor NFkappa-B pathway. Our data also demonstrate for the first time that neuroinflammation is associated with long term MA-intoxication. Chronic MA administration produces self-limited sub-chronic neuroinflammatory response which is manifested by robust but transient microglial activation, induction of COX-2, overproduction of prostaglandins, and long lasting astrocytosis. Our findings further suggest that excess striatal DA release may be at least partially responsible for the inflammation while macrophage migration inhibitory factor may contribute to the vanishing of microglial activation. Long term co-administration of COX inhibitors with MA can partly diminish MA-induced reduction in DAT level, however the COX inhibitors were not able to protect DAergic terminals from degeneration. Behavioral sensitization has been proposed as a model of psychostimulant-induced addiction. The effect of COX inhibitors on MA-elicited behavioral sensitization was also investigated. Our results showed that the COX-2 selective inhibitor celecoxib had no effect on MA behavioral sensitization, while the nonselective COX inhibitor indomethacin enhanced it. Additionally, our findings indicate that COX-2 does not appear to mediate MA sensitization, and elevated phosphorylation of Erk1/2 and TrkB receptor may underlie the indomethacin enhanced behavioral sensitization to MA. High dietary intake of fats is associated with cognitive decline and increased risk of dementia. Our data revealed that the brains of rats administered a high fat diet demonstrated enhanced prostaglandin E2 production and COX-2 expression. In the APP/PS1 transgenic Alzheimer's disease (AD) mouse model, we found that suppression of NFkappa-B using pyrrolidine dithiocarbamate attenuated astrogliosis but increased cerebral beta amyloid 1-42 burden. This suggests that neuroinflammation may contribute to the clearance of beta amyloid in the AD brain. In summary, neuroinflammation exists in all the animal models that we studied and the process changes with time in the MA models of toxicity. The role of neuroinflammation varies in different models and depends on the different disorders and the stages of pathology.

Download or read book Systems Biology of Free Radicals and Antioxidants written by Ismail Laher and published by Springer. This book was released on 2014-06-16 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The focus of this collection of illustrated reviews is to discuss the systems biology of free radicals and anti-oxidants. Free radical induced cellular damage in a variety of tissues and organs is reviewed, with detailed discussion of molecular and cellular mechanisms. The collection is aimed at those new to the field, as well as clinicians and scientists with long standing interests in free radical biology. A feature of this collection is that the material also brings insights into various diseases where free radicals are thought to play a role. There is extensive discussion of the success and limitations of the use of antioxidants in several clinical settings.

Download or read book Lipid Mediators written by Fiona M. Cunningham and published by . This book was released on 1994 with total page 402 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides an overview of lipid mediators from synthesis to inhibition. It addresses the immune system and its diseases from a pharmacological viewpoint and combines clinical aspects with basic science.

Download or read book Multiple Sclerosis written by Ian S. Zagon and published by . This book was released on 2017 with total page 137 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Resolution of Inflammation written by Adriano Rossi and published by Springer Science & Business Media. This book was released on 2008-03-17 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides readers with an up-to-date and comprehensive view on the resolution of inflammation and on new developments in this area, including pro-resolution mediators, apoptosis, macrophage clearance of apoptotic cells, possible novel drug developments.

Download or read book Genetics Neurology Behavior and Diet in Parkinson s Disease written by Colin R Martin and published by Academic Press. This book was released on 2020-08-13 with total page 764 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetics, Neurology, Behavior, and Diet in Parkinson's Disease: The Neuroscience of Parkinson’s Disease, Volume 2 provides a single source of material covering different scientific domains of neuropathology underlying this condition. The book covers a wide range of subjects and unravels the complex relationships between genetics, molecular biology, pharmaceutical chemistry, neurobiology, imaging, assessments, and treatment regimens. It fills a much-needed gap as a "one-stop" synopsis of everything to do with the neurology and neuroscience related to Parkinson’s disease—from chemicals and cells to individuals. It is an invaluable resource for neuroscientists, neurologists, and anyone in the field. Offers the most comprehensive coverage of a broad range of topics related to Parkinson's disease Serves as a foundational collection for neuroscientists and neurologists on the biology of disease and brain dysfunction Contains in each chapter an abstract, key facts, mini dictionary of terms, and summary points to aid in understanding Features preclinical and clinical studies to help researchers map out key areas for research and further clinical recommendations Serves as a "one-stop" source for everything you need to know about Parkinson’s disease

Download or read book Inflammation and Stroke written by Giora Z. Feuerstein and published by Springer Science & Business Media. This book was released on 2001 with total page 664 pages. Available in PDF, EPUB and Kindle. Book excerpt: New opportunities for stroke prevention and therapeutics: a hope from anti-inflammatory drugs?.- Inflammation in stroke and CNS trauma - experimental and clinical evidence.- Clinical evidence of inflammation as a risk factor in ischemic stroke.- Inflammation as a risk factor for stroke: evidence from experimental models.- Inflammatory and immune responses to CNS injury: beneficial and detrimental components.- Salutary effect of autoimmune T cells after central nervous system injury.- Traumatic brain injury: is head trauma an inflammatory disease?.- Cyclic activation and inactivation of brain vessels involving inflammatory mediators - implications for stroke.- Inflammatory cells in stroke.- Do leukocytes play a role in focal ischemia in the brain? An objective review of the literature.- The role of microglia in ischemic brain injury.- Inflammatory activation of brain cells by hypoxia: transcription factors and signaling pathways.- Inflammatory cytokines, interleukins and chemokines in stroke and CNS trauma.- Cytokine effects on CNS cells: implications for the pathogenesis and prevention of stroke.- Interleukin-10 in cerebral ischemia and stroke.- Chemokines and ischemic stroke.- Biphasic activity of tumor necrosis factor in stroke and brain trauma: interaction with reactive oxygen species.- Interleukin-1 and IL-1 receptor antagonist in stroke: mechanisms and potential therapeutics.- Inflammatory cytokines in CNS trauma.- Inflammation in cerebral thrombosis, angiogenesis and matrix regulation: a new perspective in stroke research and therapeutics.- Microvessel integrin expression during focal cerebral ischemia.- The inflammatory response in focal cerebral ischemia.- Chronic neuronal perturbation mediated by RAGE, a receptor for ?-sheet fibrils and S100/calgranulins.- Mediators of inflammation and blood-brain barrier permeability in cerebral ischemia.- Inflammatory proteases and oxygen radicals in stroke.- The role of metalloproteinases on blood-brain barrier breakdown after ischemic stroke.- Matrix metalloproteinases and their inhibitors in hypoxia/reoxygenation and stroke.- Extracellular matrix-degrading metalloproteinases and neuroinflammation in stroke.- Anti-oxidant strategies to treat stroke.- Inflammatory adhesion molecules, kinins, nitric oxide complement factors and lipid mediators in stroke.- Selectin-and complement-mediated mechanisms of tissue injury in stroke.- The kallikrein-kinin system in ischemic and traumatic brain injury.- Nitric oxide, nitric oxide synthases and cyclooxygenase-2 in experimental focal stroke.

Download or read book The Ovary written by Peter C. K. Leung and published by Academic Press. This book was released on 2018-09-10 with total page 625 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Ovary, Third Edition, includes more than 60% new material that highlights the clinical aspects of human ovarian functions. It covers advances in the areas of genomics, assisted reproductive technology, and cancer diagnosis and treatment. This updated edition synthesizes new information at the molecular, cellular and organismal levels, while also presenting modern ovarian physiology in a more understandable and comparative context. The book looks at ovarian function from a detailed molecular and cellular level that examines all phases of the ovarian lifecycle that places special emphasis on the pathophysiology of the human ovary, including ovarian carcinogenesis. Represents an unparalleled compilation of chapters that are relevant to contemporary ovarian physiology Provides basic and clinical research on ovarian function, abnormalities, assisted reproductive technology, and cancer Highlights contemporary strategies and treatment paradigms in female factor infertility

Download or read book Molecular and Genetic Basis of Renal Disease written by David B. Mount and published by Elsevier Health Sciences. This book was released on 2008-01-01 with total page 604 pages. Available in PDF, EPUB and Kindle. Book excerpt: This companion to Brenner and Rector's The Kidney offers a state-of-the-art summary of the most recent advances in renal genetics. Molecular and Genetic Basis for Renal Disease provides the nephrologist with a comprehensive look at modern investigative tools in nephrology research today, and reviews the molecular pathophysiology of the nephron as well as the most common genetic and acquired renal diseases. A comprehensive clinical review of Medelian renal disease is also be included. Detailed review of the molecular anatomy and pathophysiology of the nephron that provides relevant basic science to consider when diagnosing and managing patients with these disorders.

Download or read book PH and Brain Function written by Kai Kaila and published by John Wiley & Sons. This book was released on 1998-09-15 with total page 694 pages. Available in PDF, EPUB and Kindle. Book excerpt: "PH and Brain Function offers thorough coverage of this increasingly important area of research, beginning with the fundamental concepts, which include methodological and theoretical issues such as the measurement of pH and the concept of pH in neurobiology. It explores aspects of regulation and modulation of intracellular pH in brain cells, surveys the changes in pH that occur with neural activity and how these changes affect neural activity, and discusses the role of pH in the pathophysiology of neurological diseases." "pH and Brain Function is an important resource for researchers in all areas of neuroscience as well as cell biology and physiology." --Book Jacket.

Download or read book Rodent Models of Stroke written by Ulrich Dirnagl and published by Humana Press. This book was released on 2010-07-08 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In view of the numerous failures of clinical trials aimed at improving stroke therapy, the role and potential benefit of experimentally modeling focal cerebral ischemia in rodents has been debated. When methods of systematic review and metaanalyis are applied, however, it turns out that experimental models actually faithfully predicted the negative outcomes of clinical trials. In addition, thrombolysis and neuroprotection by hypothermia, first described in animal models, are key examples of treatment modalities that have made it successfully into clinical practice. In Rodent Models of Stroke, an international consortium of authors aims at critically addressing the issues on a very practical level, from choosing the model and outcome measures, designing the experiment, conducting and analyzing it, to reporting it in a scientific publication. The structure and content of the book reflect both the authors’ longstanding expertise in experimental and clinical stroke research and their roles in training the scientific community in the tools of the trade. As a volume in the successful Neuromethods series, the chapters provide authoritative reviews of the most commonly used, well-honed approaches in the field today. Stimulating and easy-to-use, Rodent Models of Stroke will help its readers understand the limitations and the opportunities of modeling stroke in rodents and enable them to conduct experiments which will not only improve our understanding of the pathophysiology of this devastating disorder but also serve as the basis for developing new highly effective treatments.

Download or read book Role of the Mediterranean Diet in the Brain and Neurodegenerative Diseases written by Tahira Farooqui and published by Academic Press. This book was released on 2017-10-24 with total page 485 pages. Available in PDF, EPUB and Kindle. Book excerpt: Role of the Mediterranean Diet in the Brain and Neurodegenerative Disease provides a comprehensive overview of the effects of all components of the Mediterranean diet on the brain, along with its beneficial effects in neurodegenerative diseases. It covers topics on neurodegenerative diseases (Alzheimer disease (AD), Parkinson disease, (PD) Huntington disease (HD) and Amyotrophic Lateral Sclerosis (ALS), also providing information on how cardiovascular disease, Type 2 Diabetes, and Metabolic Syndrome become risk factors for neurodegenerative diseases. This book focuses on how the Mediterranean diet suppresses oxidative stress and neuroinflammation in neurodegenerative diseases as well as signal transduction. The Mediterranean diet is characterized by the abundant consumption of olive oil, high consumption of plant foods (fruits, vegetables, pulses, cereals, nuts and seeds); frequent and moderate intake of wine (mainly with meals); moderate consumption of fish, seafood, yogurt, cheese, poultry and eggs; and low consumption of red meat and processed meat products. High consumption of dietary fiber, low glycemic index and glycemic load, anti-inflammatory effects, and antioxidant compounds may act together to produce favorable effects on health status. Collective evidence suggests that Mediterranean diet not only increases longevity by lowering cardiovascular disease, inhibiting cancer growth, but also by protecting the body from age-dependent cognitive decline. Comprehensively provides an overview of the effects of the Mediterranean diet on the brain and its beneficial effects in neurodegenerative diseases Discusses the relationship among Type 2 Diabetes, Metabolic Syndrome and Alzheimer's Disease, and the effect of the Mediterranean diet on normal aging, longevity, and other neurodegenerative diseases Focuses on how the Mediterranean diet suppresses oxidative stress and neuroinflammation in neurodegenerative disease

Download or read book Translational Research in Traumatic Brain Injury written by Daniel Laskowitz and published by CRC Press. This book was released on 2016-04-21 with total page 388 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Download or read book Perioperative Care of the Elderly written by Gabriella Bettelli and published by Cambridge University Press. This book was released on 2017-11-16 with total page 386 pages. Available in PDF, EPUB and Kindle. Book excerpt: This innovative, comprehensive book covers the key elements of perioperative management of older patients. The book's chapter structure coincides with the clinical path patients tread during their treatment, from preoperative evaluation to post-hospital care. Epidemiological aspects and aging processes are illustrated, providing keys to understanding the quick expansion of geriatric surgery and defining the clinical profile of older surgical patients in a cybernetic perspective. Preoperative evaluation and preparation for surgery, including medication reconciliation and pre-habilitation, are developed in the light of supporting decision-making about surgery in an evidence-based and patient-focused way. Intra- and postoperative management are discussed, aiming to tailor anesthetic, surgical and nursing approaches to specific patients' needs, in order to prevent both general and age-related complications. This volume also addresses issues relevant to geriatric surgery, from different organizational models to clinical risk management and systems engineering applied to hospital organization.

Download or read book Biology of C Reactive Protein in Health and Disease written by Waliza Ansar and published by Springer. This book was released on 2016-03-23 with total page 324 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book offers a comprehensive study of C-reactive protein (CRP) belonging to the pentraxin family, including a brief history of CRP, its structure, synthesis and evolution. Focusing on the emerging role of CRP and its clinical application in the field of disease biology, it details the pathophysiological role of CRP in a host of diseases such as cardiovascular disease, diabetes, cancers, rheumatoid arthritis and infectious diseases and others. It also discusses the role of innate immunity and acute phase response (APR) and their key mediators in the host body in response to tissue injury, infection, trauma or surgery, immunological disorders or neoplastic growth. CRP’s significance in inflammation is highlighted, and its importance as a clinical marker in cardiovascular disease, its functional significance in Leishmania and Plasmodium infections, its association with the development of insulin resistance in type 2 diabetes mellitus, and its role in cancer are discussed in detail. The book also includes clinical data studies and presents the latest research advances to further readers’ understanding of CRP.

Download or read book The Eicosanoids written by Peter Curtis-Prior and published by John Wiley & Sons. This book was released on 2004-07-16 with total page 654 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive reference work, updated from the first edition, brings together the knowledge and expertise of contributors from around the world. It includes new topics such as prostaglandin synthetase enzyme, new synthetic eicosanoids, innovative analytical methods, the influence of cytokines in the regulation of synthesis and actions, newer eicosanoids that influence the cardiovascular system, and newly discovered roles in reproduction and interactions with nitric oxide. This book satisfies a surge of interest in prostaglandins—NSAIDS (e.g. aspirin) are the biggest selling drugs of all time, and the field has been refreshed by the advent of new types (selective COX-2 inhibitors, anti-leukotiene drugs).