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The development of new CNS drugs is notoriously difficult. Drugs must reach CNS target sites for action and these sites are protected by a number of barriers, the most important being the blood –brain barrier (BBB). Many factors are therefore critical to consider for CNS drug delivery, e.g. active/passive transport across the BBB, intra-brain distribution, and central/systemic pharmacokinetics, to name a few. Neurological disease and trauma conditions add further complexity because CNS barriers, drug distribution and pharmacokinetics are dynamic and often changed by disease/trauma. Knowledge of all these factors and their interplay in different conditions is of utmost importance for proper...
The blood-brain barrier serves to protect the brain from toxic substances whilst simultaneously allowing access to essential nutrients and chemical signals. At the interface between brain and body, knowledge of the blood-brain barrier forms an essential component in the complete understanding of a large proportion of medical disciplines. Nevertheless, it seems that ignorance of both the biology of this important membrane and the methodology suitable for its investigation still remains an impediment to progress in many fields, including, for example, the development of new and efficacious neuropharmaceuticals, cerebrovascular disease, Alzheimer's disease, cerebral AIDS and brain tumours. This introduction for both researchers and clinicians across the medical sciences is intended to aid both those beginning work directly in this area and those wishing simply to be better informed when interpreting information where the blood-brain barrier may be involved. Advances in both methodology and biology are detailed in 50 chapters from international authorities.
Focused on central nervous system (CNS) drug discovery efforts, this book educates drug researchers about the blood-brain barrier (BBB) so they can affect important improvements in one of the most significant – and most challenging – areas of drug discovery. • Written by world experts to provide practical solutions to increase brain penetration or minimize CNS side-effects • Reviews state-of-the-art in silico, in vitro, and in vivo tools to assess brain penetration and advanced CNS drug delivery strategies • Covers BBB physiology, medicinal chemistry design principles, free drug hypothesis for the BBB, and transport mechanisms including passive diffusion, uptake/efflux transporters, and receptor-mediated processes • Highlights the advances in modelling BBB pharmacokinetics and dynamics relationships (PK/PD) and physiologically-based pharmacokinetics (PBPK) • Discusses case studies of successful CNS and non-CNS drugs, lessons learned and paths to the market
Diagnosis and Treatment of Traumatic Brain Injury will improve readers' understanding of the complexities of diagnosis and management of traumatic brain injuries. Featuring chapters on drug delivery, different treatments, and rehabilitation, this volume discusses in detail the impact early diagnosis and effective management has on the long-term prognosis of these injuries and the lives of those affected. This book will be relevant for neuroscientists, neurologists, clinicians, and anyone working to better understand these injuries. Traumatic brain injury has complex etiology and may arise as a consequence of physical abuse, violence, war, vehicle collisions, working in the construction indus...
Traumatic brain injury has complex etiology and may arise as a consequence of physical abuse, violence, war, vehicle collisions, working in the construction industry, and sports. Cellular, Molecular, Physiological, and Behavioral Aspects of Traumatic Brain Injury will improve readers' understanding of the detailed processes arising from traumatic brain injury. Featuring chapters on neuroinflammation, metabolism, and psychology, this volume discusses the impact of these injuries on neurological and body systems to better understand underlying pathways. This book will be relevant for neuroscientists, neurologists, clinicians, and anyone working to better understand traumatic brain injury. - Summarizes the neuroscience of traumatic brain injury, including cellular and molecular biology - Contains chapter abstracts, key facts, dictionary, and summary points to aid in understanding - Features chapters on signaling and hormonal events - Includes plasticity and gene expression - Examines health and stress behaviors after traumatic brain injury
A vast number of diagnostic and therapeutic decisions are based on measuring blood concentrations of molecules, yet most biochemical and pharmacological events actually take place in the tissues. Microdialysis is a key semi-invasive sampling technique to measure in vivo drug penetration to the target site in humans, the method being feasible in virtually every organ. Authored by international experts in this cutting edge field, this book will provide a comprehensive overview of microdialysis and its application for measuring drug distribution in drug development.
This book discusses basics of brain diseases and the role of nanobiotechnology in existing treatment options for neurodegenerative disorders. It begins with an overview of brain diseases and the need for novel drug-delivery approaches. It highlights the current route for the intranasal advanced drug-delivery systems for brain diseases. It also discusses innovative categories of drug-delivery systems, including mesoporous silica nanoparticles, polymeric nanocarriers, and lipid-based nanocarriers through multi-responsive DDSs and their implications in brain disorders. Features: Includes an overview of brain diseases and highlights the need for novel drug-delivery approaches Focuses on theoreti...
During the past three decades, the cerebral vasculature and its role in blood-brain transport has been an increasingly active area of investigation and learning, particularly from an anatomical and physiological point of view. However, much less is known at the molecular and cellular level about the blood-brain barrier especially regarding the macromolecules responsible for transport, the roles played by vascular wall components (endothelial cell, pericyte, smooth muscle, basement membrane), and the mechanisms regulating brain vascular-specific protein expression and their molecular alterations during development and disease. Fundamental questions still unanswered include: What are the molec...
Microdialysis is currently one of the most important in vivo sampling methods in physiology and pharmacology. It is used to determine the chemical components of the fluid in the extracellular space of tissues. The technique is now well established in neuroscience research and is used excessively in behavioral neuroscience to determine the concentrations and identities of molecules in brain tissues, and their change due to behavior, hormonal and transmitter changes in the nervous system. The book provides a detailed comprehensive overview of the technology and its applications, including application in pathology, drug development, and the application in the clinic. The authors are all well kn...
This comprehensive volume provides an update on the current state of pharmacometrics in drug development. It consists of nineteen chapters all written by leading scientists from the pharmaceutical industry, regulatory agencies and academia. After an introduction of the basic pharmacokinetic and pharmacodynamic concepts of pharmacometrics in drug development, the book presents numerous examples of specific applications that utilize pharmacometrics with modeling and simulations over a variety of therapeutic areas, including pediatrics, diabetes, obesity, infections, psychiatrics, Alzheimer’s disease, and dermatology, among others. The examples illustrate how results from all phases of drug d...