Brain Tight

This e-book will review special features of the cerebral circulation and how they contribute to the physiology of the brain. It describes structural and functional properties of the cerebral circulation that are unique to the brain, an organ with high metabolic demands and the need for tight water and ion homeostasis. Autoregulation is pronounced in the brain, with myogenic, metabolic and neurogenic mechanisms contributing to maintain relatively constant blood flow during both increases and decreases in pressure. In addition, unlike peripheral organs where the majority of vascular resistance resides in small arteries and arterioles, large extracranial and intracranial arteries contribute significantly to vascular resistance in the brain. The prominent role of large arteries in cerebrovascular resistance helps maintain blood flow and protect downstream vessels during changes in perfusion pressure. The cerebral endothelium is also unique in that its barrier properties are in some way more like epithelium than endothelium in the periphery. The cerebral endothelium, known as the blood-brain barrier, has specialized tight junctions that do not allow ions to pass freely and has very low hydraulic conductivity and transcellular transport. This special configuration modifies Starling's forces in the brain microcirculation such that ions retained in the vascular lumen oppose water movement due to hydrostatic pressure. Tight water regulation is necessary in the brain because it has limited capacity for expansion within the skull. Increased intracranial pressure due to vasogenic edema can cause severe neurologic complications and death.

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 development of new diagnostic and therapeutic approaches has been disappointingly slow. Translational Research in Traumatic Brain Injury attempts to integrate expertise from across specialties to address knowledge gaps in the field of TBI. Its chapters cover a wide scope of TBI research in five broad areas: Epidemiology Pathophysiology Diagnosis Current treatment strategies and sequelae Future therapies Specific topics discussed include the societal impact of TBI in both the civilian and military populations, neurobiology and molecular mechanisms of axonal and neuronal injury, biomarkers of traumatic brain injury and their relationship to pathology, neuroplasticity after TBI, neuroprotective and neurorestorative therapy, advanced neuroimaging of mild TBI, neurocognitive and psychiatric symptoms following mild TBI, sports-related TBI, epilepsy and PTSD following TBI, and more. The book integrates the perspectives of experts across disciplines to assist in the translation of new ideas to clinical practice and ultimately to improve the care of the brain injured patient.

The brain ... There is no other part of the human anatomy that is so intriguing. How does it develop and function and why does it sometimes, tragically, degenerate? The answers are complex. In Discovering the Brain, science writer Sandra Ackerman cuts through the complexity to bring this vital topic to the public. The 1990s were declared the "Decade of the Brain" by former President Bush, and the neuroscience community responded with a host of new investigations and conferences. Discovering the Brain is based on the Institute of Medicine conference, Decade of the Brain: Frontiers in Neuroscience and Brain Research. Discovering the Brain is a "field guide" to the brainâ€"an easy-to-read discussion of the brain's physical structure and where functions such as language and music appreciation lie. Ackerman examines: How electrical and chemical signals are conveyed in the brain. The mechanisms by which we see, hear, think, and pay attentionâ€"and how a "gut feeling" actually originates in the brain. Learning and memory retention, including parallels to computer memory and what they might tell us about our own mental capacity. Development of the brain throughout the life span, with a look at the aging brain. Ackerman provides an enlightening chapter on the connection between the brain's physical condition and various mental disorders and notes what progress can realistically be made toward the prevention and treatment of stroke and other ailments. Finally, she explores the potential for major advances during the "Decade of the Brain," with a look at medical imaging techniquesâ€"what various technologies can and cannot tell usâ€"and how the public and private sectors can contribute to continued advances in neuroscience. This highly readable volume will provide the public and policymakersâ€"and many scientists as wellâ€"with a helpful guide to understanding the many discoveries that are sure to be announced throughout the "Decade of the Brain."

The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.

Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.

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

Neurodegenerative diseases, such as a stroke, Alzheimer's and dementia, are now tragically commonplace within the western world. Our brains are a strange and complex organ, and there is much to be discovered about what causes them to fail in such devastating ways. In this book Kathleen Taylor presents the ever-developing research into the cause and cure of these life-changing conditions, focusing on insights arising from the relatively new field of neuroimmunology - the increasing recognition of the important role of the immune system in the brain. Interweaving the latest scientific ideas on neurodegenerative diseases with accounts of the devastation which illnesses affecting the brain can cause to sufferers and to anyone who cares about them, The Fragile Brain is not only an important account of current research in this field, but a very personal study. As instances of dementia rise in our ageing populations, many harbour anxieties concerning the future.This book is about knowing the enemy.

Denis Noble Nearly a decade after completion of the first draft of the entire Human Genome sequence we are in a better position to assess the nature and the consequences of that heroic achievement, which can be seen as the culmination of the molecular biological revolution of the second half of the twentieth century. The achievement itself was celebrated at the highest levels (President and Prime Minister) on both sides of the Atlantic, and rightly so. DNA sequencing has become sufficiently c- mon now, even to the extent of being used in law courts, that it is easy to forget how technically difficult it was and how cleverly the sequencing teams solved those problems in the exciting race to finish by the turn of the century [1, 2]. The fanfares were misplaced, however, in an important respect. The metaphors used to describe the project and its biological significance gave the impression to the public at large, and to many scientists themselves, that this sequence would reveal the secrets of life. DNA had already been likened to a computer program [3]. The “genetic program” for life was therefore to be found in those sequences: A kind of map that had simply to be unfolded during development. The even more colo- ful “book of life” metaphor gave the promise that reading that book would lead to a veritable outpouring of new cures for diseases, hundreds of new drug targets, and a brave new world of medicine.