New Therapeutics for Traumatic Brain Injury

Prevention of Secondary Brain Damage and Enhancement of Repair and Regeneration
 
 
Academic Press
  • 1. Auflage
  • |
  • erschienen am 27. September 2016
  • |
  • 352 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
E-Book | PDF mit Adobe DRM | Systemvoraussetzungen
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978-0-12-802701-1 (ISBN)
 

New Therapeutics for Traumatic Brain Injury: Prevention of Secondary Brain Damage and Enhancement of Repair and Regeneration explores traumatic brain injury (TBI), a major cause of death and disability throughout the world. The delayed nature of the secondary injury phase suggests that there is a therapeutic window for pharmacological interventions or other approaches to prevent progressive tissue damage and improve functional outcomes. It is now apparent that therapeutic interventions should entail both protective and repair/regeneration strategies depending on the phase of brain injury.

This book describes emerging experimental strategies for the treatment of TBI, including new anti-inflammatory or anti-apoptotic therapeutics that limit brain damage, and novel or repurposed drugs that enhance repair or regeneration of the brain after injury.


  • Comprehensive overview of basic approaches and translational development of new therapies for TBI
  • Edited by a prominent TBI researcher that includes contributions by leading global researchers in the field
  • Presents a great resource for researchers and practitioners to learn more about the many evolving preclinical studies and clinical trials currently underway, and the challenges of bringing translational studies in TBI to the clinic
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 4,78 MB
978-0-12-802701-1 (9780128027011)
0128027010 (0128027010)
weitere Ausgaben werden ermittelt
  • Front Cover
  • New Therapeutics for Traumatic Brain Injury
  • New Therapeutics for Traumatic Brain Injury: Prevention of Secondary Brain Damageand Enhancement of Repair and Regeneration
  • Copyright
  • Contents
  • List of Contributors
  • Foreword
  • Preface
  • Introduction
  • I - Interventional Therapies for TBI in Phase 3 Clinical Trials
  • 1 - Why Did the Phase III Clinical Trials for Progesterone in TBI Fail? An Analysis of Three Potentially Critical Factors
  • INTRODUCTION: PROGESTERONE TREATMENT SHOWED PROMISE IN PRECLINICAL RESEARCH
  • THE PHASE II TRIALS
  • THE PHASE III TRIALS
  • FACTORS CONTRIBUTING TO THE TRIAL FAILURES
  • FURTHER ISSUES IN THE TRIAL FAILURES: DOSING, DURATION OF TREATMENT, VEHICLE EFFECTS
  • ACKNOWLEDGMENTS
  • DISCLOSURE
  • REFERENCES
  • 2 - Hypothermia for Traumatic Brain Injury: Current Evidence and Future Directions
  • INTRODUCTION
  • MECHANISMS OF PROTECTION AND POTENTIAL SIDE EFFECTS
  • MANAGEMENT STRATEGIES
  • Depth, Timing, Duration, and Rewarming
  • Methods of Cooling
  • Side Effects and Complications
  • EFFICACY STUDIES
  • Severe TBI in Adults
  • Severe TBI in Children
  • CONCLUSIONS AND FUTURE DIRECTIONS
  • REFERENCES
  • 3 - The Future of TBI: Hyperbaric Oxygen as a Primary Therapeutic Approach
  • INTRODUCTION
  • A BRIEF HISTORY OF HBOT
  • WHAT IS TRAUMATIC BRAIN INJURY?
  • Brief History
  • Traumatic Brain Injury
  • SYMPTOMS OF TRAUMATIC BRAIN INJURY
  • Acute Symptoms
  • Chronic Ailments
  • THE MILITARY AND TRAUMATIC BRAIN INJURY
  • SPORTS AND THE NATIONAL FOOTBALL LEAGUE
  • THE SCIENCE BEHIND HBOT FOR TRAUMATIC BRAIN INJURY
  • How Does It Work?
  • On the Cellular and Molecular Level
  • CLINICAL TRIALS OF HBOT FOR TRAUMATIC BRAIN INJURY
  • POTENTIAL SIDE EFFECTS AND CURRENT USE
  • CONCLUSIONS
  • REFERENCES
  • II - Repurposing FDA Approved Drugs for TBI Treatment
  • 4 - Erythropoietin and Its Derivatives: Mechanisms of Neuroprotection and Challenges in Clinical Translation
  • NEURODEGENERATION AND NEUROGENESIS AFTER TRAUMATIC BRAIN INJURY
  • ERYTHROPOIETIN AS AN ENDOGENOUS NEUROPROTECTIVE MOLECULE
  • DERIVATIVES OF ERYTHROPOIETIN
  • PRECLINICAL STUDIES OF ERYTHROPOIETIN IN STROKE
  • ERYTHROPOIETIN IN OTHER ANIMAL MODELS OF BRAIN DISEASE
  • PRECLINICAL STUDIES OF ERYTHROPOIETIN IN TRAUMATIC BRAIN INJURY
  • ERYTHROPOIETIN PROMOTES ANGIOGENESIS
  • HUMAN TRIALS WITH ERYTHROPOIETIN DURING THE ACUTE PHASE OF ISCHEMIC STROKE AND TRAUMATIC BRAIN INJURY
  • CONCLUSIONS
  • AUTHOR CONTRIBUTIONS
  • LIST OF ABBREVIATIONS
  • ACKNOWLEDGMENTS
  • REFERENCES
  • 5 - Atorvastatin in the Treatment of Traumatic Brain Injury
  • INTRODUCTION
  • PHARMACODYNAMICS
  • PHARMACOKINETICS AND ADVERSE EFFECTS
  • CLINICAL INVESTIGATIONS
  • Ischemic Stroke
  • Subarachnoid Hemorrhage
  • Intracerebral Hemorrhage
  • CONCLUSION
  • REFERENCES
  • 6 - The Application of Glibenclamide in Traumatic Brain Injury
  • SULFONYLUREA RECEPTOR 1 AND ITS ROLE IN CENTRAL NERVOUS SYSTEM INJURY
  • GLIBENCLAMIDE-A POTENT INHIBITOR OF SULFONYLUREA RECEPTOR 1
  • SULFONYLUREA RECEPTOR 1 AND GLIBENCLAMIDE IN THE SETTING OF TRAUMATIC BRAIN INJURY
  • Sulfonylurea Receptor 1-Related Edema and Progressive Secondary Hemorrhage After Trauma
  • Glibenclamide in Animal Models of Traumatic Brain Injury
  • Glibenclamide and Traumatic Brain Injury in Humans
  • SUMMARY
  • ACKNOWLEDGMENTS
  • CONFLICTS OF INTEREST
  • REFERENCES
  • 7 - Perispinal Etanercept for Traumatic Brain Injury
  • BACKGROUND
  • Introduction
  • Excess Tumor Necrosis Factor as a Therapeutic Target for Treatment of Traumatic Brain Injury
  • Etanercept is Therapeutically Effective in Basic Science Models of Traumatic Brain Injury and Stroke
  • PERISPINAL ETANERCEPT FOR TREATMENT OF TRAUMATIC BRAIN INJURY
  • Delivery of Etanercept Using the Cerebrospinal Venous System
  • Perispinal Administration of Etanercept Produces Rapid Intracerebroventricular Delivery in an Experimental Model
  • Perispinal Etanercept-Clinical Development
  • Clinical Experience Using Perispinal Etanercept for Chronic Poststroke Neurological Dysfunction
  • Clinical Effects of Perispinal Etanercept for Treatment of Traumatic Brain Injury
  • Walking Improvement
  • Reduction in Spasticity
  • Motor Improvement
  • Improvement in Balance and Coordination
  • Cognitive Improvement
  • Behavioral and Psychological Improvement
  • Improvements in Speech and Language
  • Improvements in Special Senses
  • Improvement in Tactile Sensation
  • Reduction in Pain Syndromes
  • Challenges for the Future
  • REFERENCES
  • III - Interventional Drugs for TBI in Phase 1-2 Clinical Trials
  • 8 - Nitric Oxide Synthase Inhibitors in Traumatic Brain Injury
  • INTRODUCTION
  • CHANGES OF NO METABOLISM IN THE BRAIN AFTER TBI
  • NOS INHIBITORS IN EXPERIMENTAL TBI
  • TETRAHYDROBIOPTERIN ANTAGONISTS AS NOS INHIBITORS
  • VAS203 IN THE TREATMENT OF TBI
  • REFERENCES
  • 9 - Management of Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury
  • INTRODUCTION
  • NOMENCLATURE
  • INCIDENCE
  • Diagnostic Criteria
  • Risk Factors
  • Onset
  • Neuroanatomical Basis
  • MECHANISM: THEORIES
  • NEUROLOGICAL AND FUNCTIONAL OUTCOMES
  • SYSTEMIC CONSEQUENCES
  • Psychiatric Consequences
  • MANAGEMENT OF PSH
  • Adrenergic Blockade
  • ONGOING CLINICAL TRIAL
  • A FINAL CONSIDERATION
  • SUMMARY
  • REFERENCES
  • IV - Interventional Drugs for TBI in Preclinical Development
  • 10 - The Use of Estrogen for the Treatment of Traumatic Brain Injury
  • BACKGROUND
  • THE GOLDEN HOUR
  • MECHANISMS OF ESTROGEN ACTION
  • THE NEUROPROTECTIVE EFFECTS OF ESTROGENS
  • NEURONAL STRETCH ASSAY
  • MULTIPLE THERAPIES FROM ONE DRUG
  • FORMULATING A DRUG
  • ESTROGEN AND TRAUMATIC BRAIN INJURY
  • The Model System and Traumatic Brain Injury Induction Protocol
  • Lateral Fluid Percussion Induction
  • Drug Delivery
  • Combinatorial Studies
  • Evaluation of Efficacy for EE-3-SO4 in Treating Traumatic Brain Injury
  • Statistical Analyses
  • RESULTS
  • Memory and Cognition Evaluation
  • Magnetic Resonance Imaging Estimation of Edema
  • Fractional Anisotropy Estimation of Neuronal Damage
  • Positron Emission Tomography-Computed Tomography Measurement of Brain Glycolysis
  • Weight Gain
  • Physical Activity
  • Neuronal Stretch Assay
  • Brain Physiological Measurements
  • SUMMARY
  • ACKNOWLEDGMENTS
  • REFERENCES
  • 11 - Voltage-Gated Calcium Channel Blockers for the Treatment of Traumatic Brain Injury
  • TRAUMATIC BRAIN INJURY
  • TRAUMATIC BRAIN INJURY AND [CA2+]I
  • VOLTAGE-GATED CALCIUM CHANNELS
  • Voltage-Gated Calcium Channel Subtypes
  • Voltage-Gated Calcium Channel Distribution
  • Antagonism of Voltage-Gated Calcium Channel
  • NEUROPROTECTIVE EFFECTS OF VOLTAGE-GATED CALCIUM CHANNEL BLOCKERS
  • Evidence for the Role of L-Type Voltage-Gated Calcium Channel in Traumatic Brain Injury
  • Evidence for the Role of N-Type Voltage-Gated Calcium Channel in Traumatic Brain Injury
  • CHRONIC PAIN
  • CONCLUSION
  • REFERENCES
  • 12 - 5-Lipoxygenase-Activating Protein Inhibitors: Promising Drugs for Treating Acute and Chronic Neuroinflammation Following Brain Injury
  • LEUKOTRIENES
  • APPROVED ANTILEUKOTRIENE DRUGS
  • THE DISCOVERY OF 5-LIPOXYGENASE-ACTIVATING PROTEIN AND THE DEVELOPMENT OF 5-LIPOXYGENASE-ACTIVATING PROTEIN INHIBITORS
  • THE POTENTIAL USE OF 5-LIPOXYGENASE-ACTIVATING PROTEIN INHIBITORS IN ACUTE BRAIN INJURY
  • THE POTENTIAL USE OF 5-LIPOXYGENASE-ACTIVATING PROTEIN INHIBITORS IN PROLONGED NEUROINFLAMMATION FOLLOWING MILD TRAUMATIC BRAIN ...
  • CONCLUSIONS
  • REFERENCES
  • 13 - Carbonyl Scavenging as an Antioxidant Neuroprotective Strategy for Acute Traumatic Brain Injury
  • INTRODUCTION
  • BASICS OF FREE RADICAL-INDUCED LP
  • INCREASE IN LP-DERIVED ALDEHYDES 4-HNE AND ACROLEIN IN ACUTE TRAUMATIC SPINAL CORD OR BRAIN INJURY AND ASSOCIATION WITH MITOCHON...
  • COMPARATIVE EFFECTS OF 4-HNE AND ACROLEIN ON BRAIN AND SPINAL CORD MITOCHONDRIA
  • CARBONYL SCAVENGING AS AN ANTIOXIDANT NEUROPROTECTIVE STRATEGY
  • NEUROPROTECTIVE EFFECTS OF PHENELZINE IN EXPERIMENTAL TBI
  • ONGOING STUDIES ON PHENELZINE CARBONYL SCAVENGING-MEDIATED NEUROPROTECTION
  • ACKNOWLEDGMENTS
  • REFERENCES
  • 14 - TrkB Receptor Agonist 7,8-Dihydroxyflavone and Its Therapeutic Potential for Traumatic Brain Injury
  • INTRODUCTION
  • NEUROTROPHINS AND TROPOMYOSIN RECEPTOR KINASE B RECEPTOR
  • TRKB SIGNALING PATHWAYS AND ITS FUNCTION
  • THE MOLECULE 7,8-DIHYDROXYFLAVONE
  • THERAPEUTIC POTENTIAL OF 7,8-DIHYDROXYFLAVONE FOR NEUROLOGICAL DISEASES
  • CURRENT EXPERIMENTAL FINDINGS OF 7,8-DIHYDROXYFLAVONE IN THE TREATMENT OF TRAUMATIC BRAIN INJURY
  • CONCLUSION AND PERSPECTIVES
  • REFERENCES
  • 15 - Ceftriaxone Treatment of TBI
  • TRAUMATIC BRAIN INJURY AND GLUTAMATE EXCITOTOXICITY
  • GLUTAMATE PHYSIOLOGY AND HOMEOSTASIS
  • POSTTRAUMATIC CHANGES IN THE BRAIN: GLT-1, PTE, AND BEYOND
  • CEFTRIAXONE IS A SAFE, WIDELY USED ANTIBIOTIC
  • CEFTRIAXONE INCREASES GLT-1 EXPRESSION AND MITIGATES POST-TBI CONSEQUENCES
  • CEFTRIAXONE DECREASES OXIDATIVE STRESS INDEPENDENTLY OF GLUTAMATE TRANSPORT
  • CEFTRIAXONE ALTERNATIVES
  • CONCLUSION
  • REFERENCES
  • V - Drugs for TBI Rehabilitation
  • 16 - Memantine: A Safe and Tolerable NMDA Antagonist with Potential Benefits in Traumatic Brain Injury
  • INTRODUCTION
  • NMDA RECEPTORS: CRUCIAL FOR MEMORY, BUT POTENTIALLY EXCITOTOXIC
  • NMDA ANTAGONISTS VIS-À-VIS EXCITOTOXICITY IN TBI AND ISCHEMIA
  • MEMANTINE: AN NMDA ANTAGONIST WITHOUT THE UNDESIRABLE SIDE EFFECTS
  • MEMANTINE: FORMULATIONS, DOSAGES, CONTRAINDICATIONS, AND SIDE EFFECTS
  • THE POTENTIAL NEUROPROTECTIVE EFFECTS OF MEMANTINE
  • MEMANTINE IN TBI: PRECLINICAL STUDIES
  • MEMANTINE IN HUMAN TBI: EMPIRICAL STUDIES AND CONSIDERATIONS
  • CONCLUSIONS AND FUTURE DIRECTIONS
  • REFERENCES
  • 17 - Interventional Drugs for TBI Rehabilitation of Cognitive Impairment: The Cholinesterase Inhibitor Rivastigmine
  • INTRODUCTION
  • Traumatic Brain Injury: Prevalence, Affected Population, and Sequelae
  • Special Groups: Veterans as High-Risk TBI Population
  • Cognitive Impairment in TBI
  • Cholinergic Mechanism and Cognitive Impairment in TBI
  • CHOLINESTERASE INHIBITORS IN TBI
  • RIVASTIGMINE IN TBI
  • CONCLUSIONS: THE NEXT STEP(S)
  • REFERENCES
  • 18 - Docosahexaenoic Acid and Omega 3 Fatty Acids
  • Docosahexaenoic Acid and Omega 3 Fatty Acids
  • OMEGA 6 AND OMEGA 3 POLYUNSATURATED FATTY ACIDS: A BRIEF OVERVIEW
  • BRAIN DHA CONTENT IS HIGHLY CONSERVED
  • ROLE OF OMEGA-3 PUFAS IN NORMAL BRAIN DEVELOPMENT AND FUNCTION
  • ROLE OF DHA IN NORMAL NEURAL MEMBRANE COMPOSITION AND FUNCTION
  • PREEXISTING DHA DEFICIENCY WORSENS OUTCOMES AFTER EXPERIMENTAL TBI
  • POSSIBLE ROLE OF AN ACQUIRED DHA DEFICIENCY AFTER TBI
  • EFFECTS OF N-3 PUFAS ON NEUROINFLAMMATION
  • ROLE OF N-3 PUFAS IN OXIDATIVE INJURY AFTER TBI
  • OMEGA 3 PUFAS IN EXPERIMENTAL TBI
  • Pretreatment Paradigms
  • Posttreatment Paradigms
  • OMEGA 3 PUFAS IN CLINICAL TBI
  • UNANSWERED QUESTIONS AND FUTURE DIRECTIONS
  • REFERENCES
  • 19 - Treatment of Mood Disorders Following Traumatic Brain Injury
  • INTRODUCTION
  • DEPRESSIVE DISORDERS
  • Epidemiology of Depressive Disorders
  • Risk Factors of Depressive Disorders
  • Diagnosis of Depressive Disorders
  • Treatment of Depressive Disorders
  • Prevention of Depressive Disorders
  • MANIC AND MIXED MOOD DISORDERS
  • Epidemiology of Manic and Mixed Mood Disorders
  • Risk Factors of Manic and Mixed Mood Disorders
  • Diagnosis of Manic and Mixed Mood Disorders
  • Treatment of Manic and Mixed Mood Disorders
  • Future Directions
  • REFERENCES
  • Index
  • A
  • B
  • C
  • D
  • E
  • F
  • G
  • H
  • I
  • L
  • M
  • N
  • O
  • P
  • R
  • S
  • T
  • V
  • Back Cover

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