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Recent Advances in Epilepsy Research : Advances in Experimental Medicine and Biology - Devin K. Binder

Recent Advances in Epilepsy Research

Advances in Experimental Medicine and Biology

By: Devin K. Binder (Editor), Helen E. Scharfman (Editor)

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Published: 24th June 2004
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Epilepsy research has entered an exciting phase as advances in molecular analysis have supplemented in vitro and in vivo electrophysiologic and phenotypic characterization. Recent Advances in Epilepsy Research sets forth a series of chapter reviews by researchers involved in these advances. This volume is a composite profile of some exciting recent investigations in select areas of enquiry.
Key features: neurogenetics of seizure disorders, new developments in cellular and molecular neurobiology of seizure disorders, the role of growth factors in seizures, new advances in the roles of metabotropic glutamate receptors and GABA receptors and transporters, gap junctions, neuroimmunology of epilepsy, malformations of cortical development, neurogenesis, new animal models of epilepsy and the use of brain stimulation to treat epilepsy. This book should be of interest to a wide variety of audiences, including graduate students in neurobiology and related disciplines, neuroscientists, medical students, neurologists, neurosurgeons, and industry including pharmaceutical companies and medical device companies. There are many ideas in this book that will lead ingenious innovators in academia and industry to develop new and better therapies.

Genetic Approaches to Studying Mouse Models of Human Seizure Disordersp. 1
Introductionp. 1
The Knock-In Techniquep. 2
Choosing a Targetp. 2
Phenotypic Characterization of Epileptic Mutant Micep. 3
Genetic Background on Seizure Phenotypingp. 6
Summaryp. 8
Integrins, Synaptic Plasticity and Epileptogenesisp. 12
Abstractp. 12
Introductionp. 12
Integrins: Cell-Matrix and Cell-Cell Adhesion Receptorsp. 13
Integrin Expression in the Adult CNSp. 15
Adhesion Proteins Contribute to the Consolidation of Long-Term Potentiationp. 17
Seizures Activate Changes in Adhesion Chemistries: Evidence for Turnover in Adhesive Contactsp. 21
Significance of Seizure-Induced Proteolysis and Adhesion Protein Expression to Epileptogenesisp. 24
Concluding Commentsp. 26
The Role of BDNF in Epilepsy and Other Diseases of the Mature Nervous Systemp. 34
Abstractp. 34
BDNF: Introductionp. 34
BDNF Structurep. 34
BDNF Signalingp. 35
Localization, Transport and Release of BDNFp. 35
BDNF Effects in Developmentp. 36
BDNF Gene Regulationp. 36
BDNF, Synaptic Plasticity, and Learningp. 37
BDNF and Diseasep. 37
BDNF and Epilepsyp. 37
Effects of Inhibition of BDNF/trkB in Seizure Modelsp. 38
Activation of trk Receptors after Seizuresp. 42
BDNF-Induced Hyperexcitability of the Mossy Fiber-CA3 Synapsep. 44
Cellular Model of BDNF-trkB Interactionp. 45
Other Effects of BDNFp. 46
BDNF and Human Epilepsyp. 46
BDNF and Other Diseases of the Adult Nervous Systemp. 47
Summaryp. 48
Vascular Endothelial Growth Factor (VEGF) in Seizures: A Double-Edged Swordp. 57
Abstractp. 57
Introductionp. 57
Vascular Endothelial Growth Factor (VEGF)p. 58
VEGF Regulation after Seizuresp. 60
VEGF As a Neurotrophic Factorp. 62
Potential Effects of VEGF on Seizures and Their Sequelaep. 62
Plasticity Mechanisms Underlying mGluR-Induced Epileptogenesisp. 69
Abstractp. 69
Introductionp. 69
Cellular Mechanisms for Group I mGluR-Induced Excitation in Hippocampal Neuronsp. 70
Role of I[subscript mGluR(V)] in the Neuronal Activities of Single Pyramidal Cellsp. 70
Role of I[subscript mGluR(V)] in the Generation of Network Activityp. 71
Plasticity Mechanisms Underlying Group I mGluR-Induced Network Burst Dischargesp. 73
Conclusionp. 74
Role of the GABA Transporter in Epilepsyp. 76
Abstractp. 76
Introductionp. 76
Diversity of GABA Transportersp. 76
Role of the GABA Transporter in GABA Reuptakep. 77
Reversal of the GABA Transporterp. 77
Functional Significance of GABA Transporter Reversalp. 79
The GABA Transporter As a Target of Anticonvulsantsp. 83
Contribution of the GABA Transporter to Tonic GABAergic Inhibitionp. 84
Role of GABA Transporters in Epilepsyp. 87
GABA and its Receptors in Epilepsyp. 92
Abstractp. 92
Changes in the Function of GABA Neuronsp. 93
Enhanced Expression of GABA in Dentate Granule Cellsp. 94
Altered Expression of GABA[subscript A] Receptor and Its Subunits in TLEp. 95
GABA[subscript B] Receptorsp. 98
Role of the Depolarizing GABA Response in Epilepsyp. 104
Gap Junctions, Fast Oscillations and the Initiation of Seizuresp. 110
In Vitro Population Activities Paroxysmal to Greater or Lesser Extent Which Depend on Gap Junctionsp. 110
What Is the Evidence That Principal Cell Gap Junctions Exist?p. 116
How Do Axonal Gap Junctions Lead to Very Fast Oscillations?p. 116
Gap Junctions and Epileptogenesis in Vivop. 117
Summary and Unifying Hypothesesp. 117
Functional Role of Proinflammatory and Anti-Inflammatory Cytokines in Seizuresp. 123
Abstractp. 123
Introductionp. 123
Cytokine Induction by Seizuresp. 124
Pharmacological Effects: The Focus on IL-1p. 127
Proinflammatory Cytokines and Nerve Cell Injuryp. 129
Human Epileptic Tissuep. 130
Mechanism of Actionp. 130
Using the Immune System to Target Epilepsyp. 134
Introductionp. 134
Using the Immune System to Treat Neurological Disease--The Relationship between the Brain and the Immune Systemp. 134
Using the Immune System to Treat Neurological Disease--Therapeutic Agents for Neurological Diseasep. 136
Developing a Vaccine Strategy for Epilepsyp. 136
A Novel Genetic Vaccine for Stroke and Epilepsyp. 137
Concluding Remarksp. 141
Cortical Dysplasia and Epilepsy: Animal Modelsp. 145
Abstractp. 145
What Is Cortical Dysplasia?p. 145
What Are the Processes that Lead to Dysplasia?p. 149
What Makes a Dysplastic Brain (or Brain Region) Epileptic?p. 154
Seizure Variability in Dysplastic Brain--What Makes a Given Dysplastic Lesion Epileptogenic?p. 161
What Do Animal Models of Cortical Dysplasia Tell Us about Human Epilepsies?p. 163
Concluding Commentsp. 168
Malformations of Cortical Development: Molecular Pathogenesis and Experimental Strategiesp. 175
Abstractp. 175
Introductionp. 175
Important Clinical Issues in Patients with MCDp. 176
Developmental Contextual Background for MCDp. 176
Molecular Neurobiology of MCDp. 178
Epileptogenesis and MCD: How Does Cortical Maldevelopment Lead to Epilepsy?p. 183
Experimental Strategies for Studying Epilepsy in MCDp. 185
Conclusionsp. 187
Summary and New Directions: Targeted Therapy for Epilepsy in MCDp. 187
Functional Implications of Seizure-Induced Neurogenesisp. 192
Abstractp. 192
Introductionp. 192
Providing That Granule-Like Cells in the Hilus after Seizures Were Newly-Born Granule Cellsp. 194
Do All the New Granule Neurons Become Functional? Do They Behave the Same?p. 198
Is Increased Neurogenesis Beneficial, or Might It Actually Increase Seizure Susceptibility?p. 200
How Do the New Cells Interact with the Host Brain?p. 204
Is Neurogenesis Increased after Seizures in Man?p. 207
Summaryp. 207
Febrile Seizures and Mechanisms of Epileptogenesis: Insights from an Animal Modelp. 213
Abstractp. 213
Introduction: The Human Problemp. 213
The 'Optimal' Animal Modelp. 214
The Immature Rat Modelp. 217
Do Prolonged Experimental Febrile Seizures Increase Seizure Susceptibility?p. 219
Do Prolonged Experimental Febrile Seizures Cause Neuronal Death and/or Synaptic Reorganization?p. 220
Do Prolonged Experimental Febrile Seizures Alter the Rate of Granule Cell Neurogenesis?p. 220
Molecular Plasticity after Experimental Prolonged Febrile Seizuresp. 221
Summaryp. 221
The Tetanus Toxin Model of Chronic Epilepsyp. 226
Introductionp. 226
Mechanisms of Tetanus Toxinp. 226
Experimental Implementationp. 230
Chronic Epilepsy in Adult Animalsp. 230
Chronic Epilepsy in Young Animalsp. 233
Comparisons to Other Models of Chronic Epilepsyp. 235
Brain Stimulation As a Therapy for Epilepsyp. 239
Abstractp. 239
Introductionp. 239
Vagus Nerve Stimulationp. 240
DBS As a Therapy for Epilepsyp. 241
Activation of Seizure-Gating Networks--Animal Studiesp. 241
Activation of Seizure-Gating Networks--Clinical Studiesp. 242
Focal Stimulationp. 242
Selection of Stimulation Parametersp. 242
Safetyp. 243
The Future Is Now: Seizure Prediction Combined with Pre-Emptive Stimulationp. 243
Conclusionp. 244
Indexp. 249
Table of Contents provided by Rittenhouse. All Rights Reserved.

ISBN: 9780306478604
ISBN-10: 0306478609
Series: Advances in Experimental Medicine and Biology
Audience: Tertiary; University or College
Format: Hardcover
Language: English
Number Of Pages: 248
Published: 24th June 2004
Publisher: Springer Science+Business Media
Country of Publication: US
Dimensions (cm): 25.4 x 17.8  x 1.91
Weight (kg): 1.63