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Umfang: 1 online resource (1,153 pages)

Ausgabe: Second edition.

ISBN: 0-12-804067-X

Anmerkung: Cover -- Title page -- Copyright page -- Contents -- Contributors -- Foreword -- References -- Preface -- Part I - Introduction -- Chapter 1 - What Can We Model? -- Animal models of seizures -- Animal models of epilepsy -- A way forward -- References -- Chapter 2 - Comparative Biology and Species Effects on Expression of Epilepsy -- Introduction -- How does epilepsy vary across species? -- Conservative brain evolution -- Vertebrate Phylogeny -- Similarities Across Vertebrate Brains -- Brain size -- Brain Size Affects Circuitry -- Mechanisms of brain evolution -- Invasion -- Loss of Connections -- Parcellation -- Ontogenetic Buffers -- Axon Displacement -- Concerted and Mosaic Brain Evolution -- Tool for Comparing Developmental Stages Across Species -- Evolution of the neocortex and hippocampus -- Eversion of the Teleost Telencephalon -- Amphibian Dorsal Pallium -- Reptilian Dorsal Pallium -- Dorsal Ventricular Ridge of Reptiles and Birds -- Mammalian Neocortex -- Pyramidal Cell Evolution -- Neocortical Areas -- Thalamus -- Hippocampal Evolution -- Epilepsy-Relevant Species-Specific Hippocampal Characteristics -- Conclusions -- Acknowledgments -- References -- Chapter 3 - Strain Effects on Expression of Seizures and Epilepsy -- Introduction -- Mouse strain effects on expression of seizures and epilepsy -- Mouse Models of Acute Seizures and Seizure Susceptibility -- Physically-Induced Seizures -- Chemically-Induced Seizures -- Antiseizure Drugs -- The 6-Hz Psychomotor Seizure Model of Partial Epilepsy in Mice -- Mouse Strain Differences in Occurrence of Spike-Wave Discharges -- The Pilocarpine Model of Temporal Lobe Epilepsy in Mice -- The Kainate Model of Temporal Lobe Epilepsy in Mice -- The Intrahippocampal Kainate Model of Temporal Lobe Epilepsy in Mice -- The Electrical Kindling Model of Temporal Lobe Epilepsy in Mice. , The Flurothyl Kindling Mouse Model of Primary Generalized Epilepsies -- The Theiler's Virus Mouse Model of Encephalitis-Induced Temporal Lobe Epilepsy -- Rat strain effects on expression of seizures and epilepsy -- The Pilocarpine Model of Temporal Lobe Epilepsy in Rats -- The Electrical Kindling Model of Temporal Lobe Epilepsy in Rats -- Sustained Stimulation of the Basolateral Amygdala in Rats as a Model of Temporal Lobe Epilepsy -- Rat Strain Differences in Occurrence of Spike-Wave Discharges or Other EEG Alterations -- Dissection of genes that may underlie differences in expression of seizures or epilepsy -- Signal-Recognition-Particle Assembly 9 (Srp9) -- Potassium Voltage-Gated Channel Subfamily J Member 10 (Kcnj10) -- Multiple PDZ Domain Crumbs Cell Polarity Complex Component (Mpdz) -- Cholinergic Receptor Genes -- Conclusions -- Acknowledgments -- References -- Further Reading -- Chapter 4 - Good Welfare Practice in Modeling Seizures and Epilepsy -- General description -- Background -- Ethics and animal research -- Legal Framework -- NC3Rs report on welfare in rodent epilepsy models -- Intrinsic features of epilepsy models -- Seizures -- Comorbidities -- Assessing Harms and Wellbeing -- Incidental Harms -- Housing and Husbandry -- Conclusions -- References -- Chapter 5 - Ethics in the Use of Animal Models of Seizures and Epilepsy -- Introduction -- The nature of biomedical animal research ethics -- Why investigators should care about biomedical animal research ethics -- Investigators Are Already Committed to High Ethical Standards -- Ethical Treatment of Animals is Essential for Public Support -- Ethical Treatment of Animals is Required by Law -- General Commitment to Ethical Behavior -- Legal Requirements Reflecting General or Specific Ethical Principles -- Ethical Treatment of Animals is Required by Funding Agencies. , Ethical Treatment of Animals Promotes Sound Scientific Results -- Ethical Treatment of Animals is Required by Peer-Reviewed Journals -- Privately owned animals in seizure and epilepsy research -- The nature of basic research -- "Basic" Research as the Search for Knowledge for its Own Sake -- "Basic" Research as the Search for Fundamental, Underlying Mechanisms and Causes -- What Seizure and Epilepsy Investigators Mean by "Basic" Animal Research -- Recommendations -- Ethical aspects of animal research projects -- Use and Treatment in Experimental Procedures -- Housing and Care -- Treatment Before and After Research -- Core Principles of Biomedical Animal Research Ethics -- Ongoing questions and controversies -- Meaning and Underlying Rationale of Some of the Core Principles -- What Are "Harms" to Research Animals? -- Is Using Animals in Research a Necessary Evil, Even if it Does Not Cause Them Pain or Distress, and Is There an Ethical Obl... -- Other Ethical Issues -- How Should Seizure and Epilepsy Investigators Respond to These Issues? -- Minimization of Pain, Distress, and Other Harms in Animal Seizure and Epilepsy Research -- The Importance of the Pain, Distress, and Harm Minimization Principles -- When Pain, Distress, or Other Harms Are Unavoidable -- The Primacy of Project Aims -- The Pain, Distress, and Harm Justification Principles -- Problematic Expressions of the Harm Justification Principle -- Why the Harm Justification Principle, Properly Interpreted, Should Not Require Likely Benefits -- Two Unsatisfactory Responses to the Requirement of Likely Benefits -- Suggestions for Applying the Harm Justification Principle to Seizure and Epilepsy Research -- Confirm the Need to Use Animals and the Species and Numbers Employed in the Project. , Estimate any Pain, Distress, or Other Severe Harms the Animals Might Experience as Accurately and Sympathetically as Possible -- If Pain, Distress, or Other Severe Harms are Necessary for Experimental Aims, Take all Reasonable Steps to Assure That They... -- Confirm the High Medical Value of the Project -- Maximize the Scientific Value of the Project -- Predictability of Results and Scientific Value -- Engage in or Encourage Research Aimed at Improving the Translation of Animal Seizure and Epilepsy Experiments to Treatments... -- References -- Chapter 6 - Regulatory Aspects for Drug Development -- Overview of the drug development process -- Overview of the Regulatory Process -- Regulatory Guidances and Harmonization -- Good Laboratory, Clinical, and Manufacturing Practices -- What Is an IND? -- IND Exemptions -- Content of an IND Application and the IND Process -- Preclinical Pharmacology and Toxicology Studies -- Pharmacology Studies to Support Antiseizure Activity -- Seizure Tests for Drug Screening -- Chemoconvulsive Seizure Tests -- Partial Seizure Models -- Generalized Seizure Models -- Status Epilepticus Models -- Animal Models for Drug-Resistant Seizures -- Animal Models for Antiepileptogenesis and Disease Modification -- Mechanism of Action, Target Engagement, and Pharmacodynamic Studies -- Biomarkers and Target Engagement -- Pharmacodynamics of Parent Compound and Major Metabolites -- Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Studies -- Safety and Toxicology Testing -- Safety Pharmacology (CNS Adverse Effect Testing) -- Toxicology Testing -- Toxicokinetic (TK) Studies -- Chemistry, Manufacturing, and Controls -- Clinical Information -- Previous Human Experience -- Administrative Information -- Repurposing of an approved drug -- Epilepsy Syndromes as Rare Disorders -- Conclusions -- References. , Chapter 7 - Use of Animal Models for Epilepsy Research and Therapy Development -- Introduction -- Assessing the evolving needs of the patient with epilepsy -- Models used to address the unmet medical needs -- Pharmacoresistant Epilepsy -- Low-Frequency 6 Hz Seizure Test at 44 mA Stimulus Intensity -- Lamotrigine-Resistant Amygdala-Kindled Rat -- Intrahippocampal Kainic Acid Mouse Model of Mesial Temporal Lobe Epilepsy -- Inflammation in Epilepsy -- Pediatric Epilepsy Models -- Nonmammalian Genetic Models of Epilepsies -- Disease Modification and Models of Epileptogenesis -- Assessing the Predictive Validity of Animal Models -- Conclusions -- References -- Part II - Technical and Methodological Issues -- Chapter 8 - Monitoring for Seizures in Rodents -- Introduction -- Reasons for monitoring -- Epilepsy Present: Yes or No -- Equipment -- Video Recording -- Cameras -- Recording -- EEG Recording -- Radiotelemetry -- Hardwired EEG -- EEG Machines -- Digitization Frequency -- Connecting the animal to the EEG machine -- Electrical Commutators -- Cables to the Animals -- Cages -- Electrical Artifact -- Surgical/Implantation Issues -- Electrodes -- Connectors -- Implantation -- Headset Resin -- Specific Issues for Age and Species -- Summary -- Questions to ask in deciding which methods to use to document seizures in rodents -- References -- Chapter 9 - Behavioral Characterization and Scoring of Seizures in Rodents -- Introduction -- Normal behavior and factors influencing the behavior -- Light/Dark Cycle -- Animal Husbandry -- Temperature -- Stress -- Sex and the Hormonal Changes -- Strain Differences -- How to recognize a behavioral seizure? -- Convulsive Seizures -- Myoclonic Seizures -- Clonic Seizures (Synonym: Forebrain Seizures) -- Tonic-Clonic Seizures (Synonyms: Hindbrain/Brainstem, Grand Mal Seizures) -- Barrel Rotations -- Nonconvulsive Seizures. , Atypical Behavior.

Weitere Ausg.: ISBN 0-12-804066-1

Sprache: Englisch