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This volume focuses on contemporary approaches for delivering experimental and therapeutic agents into the brain. The contributions provide methodological details that are typically not available in the literature. Subtleties and shortcuts critical to each procedure are included to facilitate their use by both the experienced researcher and novice.Highlights* Polymeric, cellular, and molecular drug delivery* Neuropharmacology* Blood-brain barrier* Central nervous system
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Recent research into the anatomy and pathophysiology of the blood-brain and blood-spinal cord barriers suggests that a breakdown in these barriers can result in several diseases affecting the central nervous system (CNS). This book presents new findings in the area of blood-brain barrier research that suggest barriers play important roles in health and disease conditions. It also discusses the development of new drugs that can modulate the barrier function in the CNS and may provide new approaches to treating neurological diseases such as Alzheimer's disease and other motor neuron diseases, as
Blood-brain barrier. --- Blood-brain barrier disorders. --- Spinal cord --- Blood-vessels. --- Diseases.
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This ebook contains a series of original publications, reviews and mini-reviews by leaders in the field that address the growing importance of the plasminogen activating system in neurobiology. The articles included cover the role of the plasminogen activating system as a key modulator of blood brain barrier permeability, and the implications of this in traumatic brain injury and in ischemic stroke. State-of-the-Art manuscripts are also included that address the regulatory mechanisms that control this important process.This ebook contains a series of original publications, reviews and mini-reviews by leaders in the field that address the growing importance of the plasminogen activating system in neurobiology. The articles included cover the role of the plasminogen activating system as a key modulator of blood brain barrier permeability, and the implications of this in traumatic brain injury and in ischemic stroke. State-of-the-Art manuscripts are also included that address the regulatory mechanisms that control this important process.
blood brain barrier --- ischaemic stroke --- plasminogen activation --- Traumatic Brain Injury --- Neurobiology --- Neuroserpin --- tissue-type plasminogen activator
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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact
GBM --- DIPG --- diffuse intrinsic pontine glioma --- novel therapy --- blood-brain barrier --- drug delivery --- targeting
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Tumor immunotherapy has now shown its promise for many, its disappointments and failings for others. Going forward, brain tumor patients can both benefit and contribute. Tumor immunotherapy is steadily progressing. As experience accumulates, it is important to consider its generality. The reviews herein emphasize the brain’s place among other tumor sites. Two major topics are addressed. THE SITE: WHAT CAN WE EXPECT FROM IMMUNOTHERAPY WHEN THE TARGET IS IN THE BRAIN? Experience with immunotherapy for different targets in the brain, including tumor and also pathogens, is reviewed. Long-standing assumptions are confronted. The potential for beneficial responses is stressed. BRAIN TUMOR IMMUNOTHERAPY: WHAT HAVE WE LEARNED SO FAR? Clinical experience with brain tumor immunotherapy, from a variety of centers, is reviewed. Primary tumors, emphasizing glioblastoma, and brain metastases are each considered.
blood-brain barrier --- tumor antigen --- brain immunology --- glioblastoma --- brain tumor immunotherapy --- brain metastases --- brain tumor --- immune privilege
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The brain functions within an internal environment that is determined and controlled by morphological structures and cellular mechanisms present at interfaces between the brain and the rest of the body. In vertebrates these interfaces are across cerebral blood vessels (blood-brain barrier) choroid plexuses (blood-cerebrospinal fluid barrier) and pia-arachnoid. There is a CSF-brain barrier in the neuroepithelium lining the ventricular system that is only present in embryos. There is now substantial evidence that many brain barrier mechanisms develop early and that in some cases they are functionally more active and even more specialized compared to adult barriers. Therefore barriers in developing brain should be viewed as adapted appropriately for the growing brain and not, as is still widely believed, immature. Considerable advances in our understanding of these barrier mechanisms have come from studies of the developing brain and invertebrates. A striking aspect, to be highlighted in this special edition, is that many of the molecular mechanisms in these very diverse species are similar despite differences in the cellular composition of the interfaces. This Frontiers Topic comprises articles in three sections: Original studies, Reviews and Myths & Misconceptions. Original articles provide new information on molecular and cellular barrier mechanisms in developing brains of primates, including human embryos (Brøchner et al., Ek et al., Errede et al.), rodents (Bauer et al., Liddelow, Strazielle & Ghersi-Egea, Saunders et al., Whish et al.), chick (Bueno et al.) and zebrafish (Henson et al.) as well as studies in drosophila (Hindle & Bainton, De Salvo et al., Limmer et al.). The Reviews section includes evolutionary perspectives of the blood-brain and blood-CSF barriers (Bueno et al., Bill & Korzh). There are also detailed reviews of the current state of understanding of different interfaces and their functional mechanisms in developing brain (Bauer et al., Strazielle & Gjersi-Egea, Liddelow, Richardson et al., Errede et al., Henson et al., Brøchner et al.) and in invertebrates (Hindle & Bainton, De Salvo et al., Limmer et al). Different aspects of the relationship between properties of the internal environment of the brain and its development are discussed. (Stolp & Molnar, Johansson, Prasongchean et al.). A neglected area, namely barriers over the surface of the brain during development is also covered (Brøchner et al.). Clinically related perspectives on barrier disruption in neonatal stroke are provided by Kratzer et al. and other aspects of dysfunction by Morretti et al. and by Palmeta et al. on the continuing problem of bilirubin toxicity. Progress in this field is hampered by many prevailing myths about barrier function, combined with methodologies that are not always appropriately selected or interpreted. These are covered in the Misconceptions, Myths and Methods section, including historical aspects and discussion of the paracellular pathway, a central dogma of epithelial and endothelial biology (Saunders et al.) and a review of markers used to define brain barrier integrity in development and in pathological conditions (Saunders et al.). Use of inappropriate markers has caused considerable confusion and unreliable interpretation in many published studies. Torbett et al. deal with the complexities of the new field of applying proteomics to understanding blood-brain barrier properties as do Huntley at al. with respect to applying modern high throughput gene expression methods (Huntley et al.). The Editorial summarizes the contributions from all authors. This includes mention of some the main unanswered but answerable questions in the field and what the impediments to progress may be.
zebra fish --- development --- Influx mechanisms --- Tight Junctions --- Drosophila --- Efflux mechanisms --- blood-CSF barrier --- Choroid Plexus --- Blood-Brain Barrier
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This book describes the different approaches for drug delivery to the brain with an emphasis on the physiology of the blood-brain barrier (BBB) and the governing principles and concepts for drug delivery across the BBB. It contains cutting-edge methods for studying drug delivery and administering drugs into the brain. The book also explores different approaches for predicting human brain concentrations as well as the influence of disease and drug industry perspectives. In addition to wide-ranging coverage of physiological concepts relevant to central nervous system (CNS) drug delivery, a detailed review of brain structure, function, blood supply and fluids is also provided. In each chapter, descriptions of future challenges and unresolved questions are combined with points for discussion. This unique combination of material makes this book a valuable resource for students and for established academic and industry scientists looking to learn about state-of-the-art drug delivery research. It is also a source for stimulating new ideas among experts already performing CNS drug delivery research or working in related areas. Margareta Hammarlund-Udenaes (Ph.D.) is a Professor in Pharmacokinetics and Pharmacodynamics (PK/PD) at Uppsala University and the Head of the Translational PK/PD Group. Her research is focused on studying pharmacokinetic aspects of BBB transport of drugs in relation to CNS effects, and it has led to the development of new concepts and methods within the BBB transport area, focusing on unbound drug relationships. Elizabeth C.M. de Lange (Ph.D.) is Head of the Target Site Equilibration Group at the Division of Pharmacology of the Leiden Academic Center for Drug Research (LACDR). Her research program focuses on the development of generally applicable predictive PK/PD models on CNS drugs using advanced in vivo animal models and mathematical modeling techniques, with a number of recent successes. Robert G. Thorne (Ph.D.) is an Assistant Professor in Pharmaceutical Sciences at the University of Wisconsin-Madison School of Pharmacy. He was previously a research scientist and faculty member in the Department of Physiology & Neuroscience at the New York University School of Medicine. His research focuses on diffusive and convective transport within the CNS and the development, refinement and optimization of strategies for delivering biologics into the brain.
Drug delivery systems. --- Absorption (Physiology) --- Delivery systems, Drug --- Drug administration technology --- Drug delivery technology --- Drugs --- Delivery systems --- Blood-brain barrier. --- Brain -- Diseases -- Hormone therapy. --- Brain -- Diseases -- Immunotherapy. --- Neuropharmacology --- Blood-brain barrier --- Drug delivery systems --- Blood-Brain Barrier --- Drug Design --- Central Nervous System Agents --- Medicine. --- Pharmaceutical technology. --- Biomedicine. --- Pharmaceutical Sciences/Technology. --- Biomedicine general. --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Pharmaceutical laboratory techniques --- Pharmaceutical laboratory technology --- Technology, Pharmaceutical --- Technology --- Health Workforce --- Biomedicine, general.
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When Ehrlich discovered the first evidence of the blood-brain barrier in 1885, he probably did not perceive the Great Wall that remained hidden from consciousness inside the central nervous system. Ehrlich had observed that acidic vital dyes did not stain the brain if they were injected into the blood stream. A century ago (1913), Goldman showed that the injection of trypan blue in the cerebrospinal fluid stained only the brain, but not the other organs. For almost a century it was thought that the blood-brain barrier (BBB) consisted in a physical barrier, resulting from the restricted permeability of the cerebral endothelial cell layer, as they are joined by tight junctions. However, as scientists are always looking for news in what is already discovered, in the end of the 20th century we had evidences that cerebral endothelial and glial cells express several drug metabolizing enzymes consisting in a second protection system: a metabolic barrier. Furthermore, the drugs and their metabolites must overcome the activity of several multidrug resistance proteins that function as ATP-dependent efflux pumps, consisting in the third line of defence: the active barrier. Therefore, the way the BBB actually works should be better explained. Several endogenous compounds, as well as xenobiotics, may be activated by enzymes of the metabolic barrier, generating reactive oxygen species that could damage neurons. Therefore, endothelial and glial cells possess endogenous protecting compounds and enzymes against oxidants, consisting in an antioxidant barrier. When all these systems fail, glial cells, mainly microglia, secrete cytokines in an attempt to crosstalk with defence cells asking for help, which consists in an immune barrier. In cerebral regions that are devoid of the physical barrier, such as circumventricular organs, the metabolic, active, antioxidant and immune barriers are reinforced. It is important to understand how cells involved in the BBB interact with one another and the dynamic mechanisms of their functions. This Research Topic published in this e-Book considers recent highlights in BBB structure, cell and molecular biology, biotransformation, physiology, pathology, pharmacology, immunology and how these basic knowledges can be applied in drug discovery and clinical researches, rewriting what is already written, and paving the way that goes to the Great Wall in the Frontiers of the Brain in this new century that is just beginning.
Neuroscience --- Human Anatomy & Physiology --- Health & Biological Sciences --- glial cells --- Stroke --- Cerebral endothelial cells --- BBB --- Oxidative Stress --- Glioma --- Blood Brain Barrier --- xenobiotic metabolizing enzymes --- Parkinsons disease --- Neuroinflammation
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Blood-brain barrier. --- Blood-cerebral barrier --- Blood-cerebrospinal fluid barrier --- Brain-blood barrier --- Hemato-encephalic barrier --- Hematoencephalic barrier --- Brain --- Cerebrospinal fluid --- Choroid plexus --- Blood-vessels
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Blood-brain barrier. --- Blood-cerebral barrier --- Blood-cerebrospinal fluid barrier --- Brain-blood barrier --- Hemato-encephalic barrier --- Hematoencephalic barrier --- Brain --- Cerebrospinal fluid --- Choroid plexus --- Blood-vessels --- Barrera hematoencefàlica --- Farmacologia
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