Molecular Physiology and Metabolism of the Nervous System

Gary A. Rosenberg, MDChairman of NeurologyProfessor of Neurology, Neurosciences, Cell Biology and Physiology, and Mathematics and StatisticsUniversity of New Mexico Health Sciences CenterAlbuquerque, NM

"Molecular Physiology and Metabolism of the Nervous System is logically presented to introduce the reader to the physiology and anatomy of the cerebrospinal and interstitial fluids for understanding the pathophysiology of brain edema and other current topics such as hypoxic/ischemic brain damage and disorders of the cerebrospinal circulation. In addition, there are chapters that explore novel concepts of the neuro(glio)vascular unit and the evolvingstory of vascular cognitive impairment in Alzheimer's disease he book is oriented completely to the human brain and is, thus, especially appropriate for clinical education. The writing style is compact, yetflowing and provides more than a comprehensive entry level basic approach, but also the second level content often missing from similar style works in other areas." -- Joseph C. LaManna, PhD, Department of Physiology & Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH"Dr. Gary Rosenberg has artfully crafted a monograph, Brain Molecular Physiology and Metabolism, on how the brain and its blood supply and cerebrospinal fluid circulation work at a cellular level. The book is written by a research scientist who is also an experienced clinician. The writing is aimed at clinicians helping them to understand brain physiology. Brain images and neuropathology specimens show snapshots of anatomy and pathology that must besupplemented by physiology and pathophysiology for diagnosis and for grasping the nature of patient's symptoms and signs. Rosenberg's book ably fills this gap which is so crucial to understanding diseasemechanisms and their management. The writing is clear and easily understood and relevant to clinicians." -- Louis R. Caplan, MD,Professor of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA"This book is an eclectic collection of the protean tastes of Dr. Rosenberg. It includes materials that are old friends such as the Krebs cycle, to the most current concepts of molecular physiology and biochemistry. Up until now, most of the most modern topics have not yet produced clinically useful discoveries. However, we can anticipate that 20 years from now some of the work that is outlined in chapters of this book will have similar effects on morbidity andmortality. In summary, this book is a useful collection of a variety of topics which I personally find extremely interesting and I hope that you will think that as well. Dr. Rosenberg and hiscolleagues have put a good deal of thought into this book, and the effort shows." -- Justin A Zivin, MD, PhD, Department of Neurosciences, UC San Diego School of Medicine, La Jolla, CA and Department of Neurology, San Diego VA Healthcare System, San Diego, CA"Molecular Physiology and Metabolism of the Nervous System describes most accurately the underlying pathophysiology of numerous neurological disorders such as Idiopathic Intracranial Hypertension, hydrocephalus, ischemic/hypoxic brain injury as well as Vascular Cognitive Impairment and Alzheimer's disease. Combining the complex knowledge in the field of molecular neurology with a clear writing style and organization makes this book an outstanding andvaluable tool not only for graduate and doctoral students, research-oriented medical professionals and neuroscientists but also for anyone interested in neurophysiology. This book is well-referenced, includesrecent scientific findings and presents the most up-to-date principles in this field. We highly recommend this exceptional work by a world leading neuroscientist and clinical neurologist." -- Paul Reiner Krafft, MD and John H. Zhang MD, PhD, Loma Linda University School of Medicine, Loma Linda, CA

• Part I: Physiology of brain fluids and blood-brain barrier ; Chapter 1: Anatomy of Fluid Interfaces that Protect the Microenvironment ; 1.1. Historical perspective ; 1.2 Cerebral microenvironment ; 1.3. Development of the brain-fluid interfaces ; 1.3.1. Neural tube, ependymal cells and stem cells ; 1.3.2. Cilated ependymal cells and CSF movement ; 1.3.3. Choroid plexuses, arachnoid and capillaries ; 1.4. Extracellular Space and Extracellular Matrix ; 1.5. Brain-Fluid Interfaces ; 1.5.1. Anatomy of the cerebral blood vessels ; 1.5.2. Brain cells interfaces with CSF at ependymal and pia ; 1.6. Dura, arachnoid and pial layers ; 1.7. What are sources of energy? ; Chapter 2: Physiology of the Cerebrospinal and Interstitial Fluids ; 2.1. Introduction ; 2.2. Proteins in the CSF ; 2.3. CSF Pressure Reflects Venous Pressure in the Right Heart ; 2.4. Formation, Circulation and Absorption of CSF ; 2.4.1. Formation of CSF by choroid plexuses ; 2.4.2. Choroid plexus and disease biomarkers in CSF ; 2.4.3. Absorption of CSF at the arachnoid villi ; 2.5. Electrolyte balance in the CSF ; 2.6. Meninges and sites of masses and infection ; 2.7. Interstitial fluid ; 2.8. Lyphatic drainage ; 2.9. Water diffusion, bulk flow if ISH and diffusion tensor imaging ; 2.10. Neuropeptides and fluid homeostasis ; 2.11. Aquaporins and water transport in the CNS ; Chapter 3: Neurovascular Unit ; 3.1. Early experiments on blood-brain barrier ; 3.2. The Neurovascular unit and tight junction proteins ; 3.3. Integrins, selectins and endothelial cell adhesion ; 3.4. Astrocytes, pericytes and basal lamina ; 3.5. Movement of substances into and out of brain ; 3.6. Glucose and amino acid transport ; 3.7. Proteases and the neurovascular unit ; 3.8. Matrix metalloproteinases (MMPs) ; 3.9. A disintegrin and metalloproteinase (ADAM) ; 3.10. Barrier systems evolved to an endothelial barrier ; Part II: Metabolism, disorders of brain fluids, and mathematics of transport ; Chapter 4: Glucose, Amino acid and Lipid Metabolism ; 4.1. Glucose metabolism ; 4.2. Amino acid neurotransmitters ; 4.3. Lipid metabolism ; 4.4. Eicosanoid metabolism ; 4.5. Hepatic encephalopathy ; 4.6. Hypoglycemia ; 4.7. Hyponatremia, osmotic demyelination and acid balance ; 4.7.1. Hyponatremia ; 4.7.2. Hyperglycemia ; 4.7.3. Acidosis ; Chapter 5: Disorders of Cerebrospinal Circulation: Idiopathic Intracranial Hypertension (IIH) and Hydrocephalus ; 5.1. Introduction ; 5.2. Clinical Features of IIH ; 5.3. Treatment of IIH ; 5.4. Hydrocephalus ; 5.5. Hydrocephalus in children ; 5.6. Adult-onset hydrocephalus ; 5.6.1. Obstructive hydrocephalus ; 5.6.2. Normal-pressure hydrocephalus ; Chapter 6: Quantification of Cerebral Blood Flow and Blood Brain Barrier Transport by NMR and PET ; 6.1. Introduction ; 6.2. Mathematical approach to cerebral blood flow and transport ; 6.2.1. Cerebral blood flow: Schmidt-Kety approach ; 6.2.2. Regional blood flow ; 6.2.3. Transport between blood and brain ; 6.3 Positron emission tomography (PET) ; 6.3.1. Single-injection external registration ; 6.3.2. Patlak graphical BBB method for autoradiography and MRI ; 6.4 Magnetic resonance imaging and spectroscopy ; 6.4.1. Multinuclear NMR ; 6.4.2. Relaxation phenomenon and the rotating frame ; 6.4.3. 31P-MRS ; 6.4.4. 13C-MRS ; 6.4.5. 1H-MRS ; Part III: Ischemia, edema and inflammation ; Chapter 7: Mechanisms of Ischemic/Hypoxic Brain Injury ; 7.1. Epidemiology, risk factors and prevention of stroke ; 7.2. Molecular cascades in ischemic tissue results from energy failure ; 7.3. Excitatory and inhibitory neurotransmitters ; 7.4. Neuroinflammation in stroke ; 7.5. Proteases in hypoxia/ischemia ; 7.6. Caspases and cell death ; 7.7. Tissue inhibitors of metalloproteinases (TIMPs) and apoptosis ; 7.8. Tight junction proteins and MMPs ; 7.9. MMPs and tPA-induced bleeding ; 7.10. Animal models in stroke ; 7.11. Arteriovenous malformations and cavernous hemangiomas ; 7.12. MRI, PET and EPR in hypoxia-ischemia ; 7.12.1. MRI and MRS ; 7.12.2. Positron emission tomography (PET) ; 7.12.3. Electron paramagnetic resonance ; Chapter 8: Vascular Cognitive Impairment and Alzheimer's Disease ; 8.1. Regulation of cerebral blood flow ; 8.2. Hypoxia-ischemia in cardiac arrest ; 8.2.1 Prognosis for recovery after cardiac arrest ; 8.2.2 Cardiac surgery and memory loss ; 8.2.3 Delayed post anoxic leukoencephalopathy ; 8.3. Hypoxia inducible factors and gene expression ; 8.4. Intermittent hypoxia is a strong stimulus for HIF ; 8.5. Vascular cognitive impairment ; 8.6. White matter hyperintensities on MRI and Binswanger's disease ; 8.7. Alzheimer's disease, vascular disease and the amyloid hypothesis ; Chapter 9: Effects of Altitude on the Brain ; 9.1. Introduction ; 9.2. Genetic tolerance to altitude ; 9.3. Acute mountain sickness and high altitude pulmonary edema ; 9.4. High altitude cerebral edema ; 9.5. Cognitive consequences of hypobaric hypoxia ; 9.6. Imaging of the brain at high altitude ; 9.7. Hypoxia-inducible factors and sleep disorders in AMS ; 9.8. Treatment of altitude illnesses ; Chapter 10: Brain Edema ; 10.1. Introduction ; 10.2. Role of aquaporins in brain edema ; 10.3. Role of Neuroinflammation in the formation of vasogenic edema ; 10.3.1. Oxidative stress and brain edema ; 10.3.2 . Arachidonic acid and brain edema ; 10.3.3. Vascular endothelial growth factor and angiopoietins ; 10.4. Clinical conditions associated with brain edema ; 10.5. Imaging brain edema ; 10.6 . Treatment of brain edema and hypoxic/ischemic injury ; 10.7. Multiple drugs for treatment of ischemia ; Chapter 11: Intracerebral Hemorrhage ; 11.1. Introduction ; 11.2. History of ICH ; 11.3. Molecular mechanisms in ICH ; 11.4. Clinical aspects of intracranial bleeding ; 11.5. Pathophysiology of ICH: Evidence from animal studies ; 11.6 Extrapolation of experimental results to treatments for ICH ; Chapter 12: Autoimmunity, Hypoxia, and Inflammation in Demyelinating Diseases ; 12.1. Introduction ; 12.2. Heterogeneity of the pathological findings in MS ; 12.3. Proteases implicated in MS pathology ; 12.4. BBB disruption in MS ; 12.5. Devic's neuromyelitis optica ; 12.6. Nonimmunological processes in demyelination ; 12.7. Experimental allergic encephalomyelitis and pathogenesis of MS ; 12.8. Epilogue- synthesis and future directions