H.H. Jasper, A.A. Ward, A. Pope and H.H. Merritt, chair of the Public Health Service Advisory Committee on the Epilepsies, National Institutes of Health, published the first volume on Basic Mechanisms of the Epilepsies (BME) in 1969. Their ultimate goal was to search for a "better understanding of the epilepsies and seek more rational methods of their prevention and treatment." Since then, basic and clinical researchers in epilepsy have gathered together every decade and a half with these goals in mind -- assessing where epilepsy research has been, what it has accomplished, and where it should go. In 1999, the third volume of BME was named in honor of H.H. Jasper. In line with the enormous expansion in the understanding of basic epilepsy mechanisms over the past four decades, this fourth edition of Jasper's BME is the most ambitious yet. In 90 chapters, the book considers the role of interactions between neurons, synapses, and glia in the initiation, spread and arrest of seizures. It examines mechanisms of excitability, synchronization, seizure susceptibility, and ultimately epileptogenesis. It provides a framework for expanding the epilepsy genome and understanding the complex heredity responsible for common epilepsies as it explores disease mechanisms of ion channelopathies and developmental epilepsy genes. It considers the mechanisms of conditions of epilepsy comorbidities. And, for the first time, this 4th edition describes the current efforts to translate the discoveries in epilepsy disease mechanisms into new therapeutic strategies. This book, considered the 'bible' of basic epilepsy research, is essential for the student, the clinician scientist and all research scientists who conduct laboratory-based experimental epilepsy research using cellular, brain slice and animal models, as well as for those interested in related disciplines of neuronal oscillations, network plasticity, and signaling in brain strucutres that include the cortex, hippocampus, and thalamus. In keeping with the 1969 goals, the book is now of practical importance to the clinical neurologist and epileptologist as the progress of research in molecular genetics and modern efforts to design antiepileptic drugs, cures and repairs in the epilepsies converge and impact clinical care.

Table of Contents:
SECTION 1 INTRODUCTION 1. THE NEXT DECADE OF RESEARCH IN THE BASIC MECHANISMS OF THE EPILEPSIES 2. HERBERT H. JASPER AND THE BASIC MECHANISMS OF THE EPILEPSIES Massimo Avoli 3. Why - and how - do we approach basic epilepsy research Section II: Fundamentals of neuronal excitability relevant to seizures and epilepsy 4. Voltage-gated Na+ Channels: Structure, Function, and Pathophysiology Massimo Mantegazza and William A. Catterall 5. Potassium channels (including KCNQ) and epilepsy Edward C. Cooper 6. Voltage-gated calcium channels in epilepsy Stuart M Cain and Terrance P Snutch 7. Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channelopathy in epilepsy Nicholas P. Poolos 8. Phasic GABAA-mediated inhibition Enrico Cherubini 9. Tonic GABAA receptor-mediated signaling in epilepsy Matthew C Walker and Dimitri M Kullmann 10. Glutamatergic mechanisms related to epilepsy: ionotropic receptors Raymond Dingledine 11. Glutamate rECEPTORS IN epilepsy: Group I mGluR-MEDIATED epileptogenesis Riccardo Bianchi, Robert K. S. Wong, and Lisa R. Merlin 12. Plasticity of Glutamate Synaptic Mechanisms J. Victor Nadler 13. Neuronal synchronization and thalamocortical rhythms in sleep, wake and epilepsy Igor Timofeev, Maxim Bazhenov, Josée Seigneur, Terrence Sejnowski 14. Limbic Network Synchronization and Temporal Lobe Epilepsy John G R Jefferys, Premysl Jiruska, Marco de Curtis, Massimo Avoli 15. Imaging of Hippocampal Circuits in Epilepsy Hajime Takano and Douglas A. Coulter 16. Normal and Pathologic High-Frequency Oscillations Richard J. Staba 17. INTERICTAL EPILEPTIFORM DISCHARGES IN PARTIAL EPILEPSY: COMPLEX NEUROBIOLOGICAL MECHANISMS BASED ON EXPERIMENTAL AND CLINICAL EVIDENCE Marco de Curtis, John G R Jefferys, and Massimo Avoli 18. GABA-A RECEPTOR FUNCTION IN TYPICAL ABSENCE SEIZURES Vincenzo Crunelli, Nathalie Leresche, and David W. Cope 19. GABAB RECEPTOR AND ABSENCE EPILEPSY Hua A. Han, Miguel A. Cortez, and O. Carter Snead III 20. Brainstem networks: Reticulo-cortical synchronization in Generalized Convulsive Seizures Carl L. Faingold 21. ON THE BASIC MECHANISMS OF INFANTILE SPASMS John W. Swann and Solomon L. Moshe 22. Fast oscillations and synchronization examined with in vitro models of epileptogenesis Roger D. Traub, Miles A. Whittington, Mark O. Cunningham 23. Computer Modeling of Epilepsy Marianne J. Case, Robert J. Morgan, Calvin J. Schneider, Ivan Soltesz Section III - Mechanisms of seizures susceptibility and epileptogenesis 24. Traumatic brain injury and posttraumatic epilepsy David A. Prince, Isabel Parada, Kevin Graber 25. HEAD TRAUMA AND EPILEPSY Asla Pitkänen and Tamuna Bolkvadze 26. Fever, febrile seizures and epileptogenesis Céline M. Dubé, Shawn McClelland, ManKin Choy, Amy L. Brewster, Yoav Noam, Tallie Z. Baram 27. Role of Blood-Brain Barrier Dysfunction in Epileptogenesis Alon Friedman and Uwe Heinemann 28. Cell death and survival mechanisms after single and repeated brief seizures David C. Henshall1 and Brian S. Meldrum 29. PROGRAMMED NECROSIS AFTER STATUS EPILEPTICUS Jerome Niquet, Maria-Leonor Lopez-Meraz, Claude G. Wasterlain 30. HISTOPATHOLOGY OF HUMAN EPILEPSY Nihal C. de Lanerolle, Tih-Shih Lee, and Dennis D. Spencer 31. The Time Course and Circuit Mechanisms of Acquired Epileptogenesis F. Edward Dudeka and Kevin J. Staley 32. Mossy Fiber Sprouting in the Dentate Gyrus Paul S. Buckmaster 33. Kainate and Temporal Lobe Epilepsies: 3 decades of progress Yehezkel Ben-Ari 34. Abnormal dentate gyrus network circuitry in temporal lobe epilepsy Robert S. Sloviter, Argyle V. Bumanglag, Robert Schwarcz, and Michael Frotscher 35. Alterations in synaptic function in epilepsy Christophe Bernard 36. Seizure-induced formation of basal dendrites on granule cells of the rodent dentate gyrus Charles E. Ribak, Lee A. Shapiro, Xiao-Xin Yan, Khashayar Dashtipour, J. Victor Nadler, Andre Obenaus, Igor Spigelman, and Paul S. Buckmaster 37. Perturbations of Dendritic Excitability in Epilepsy Cha-Min Tang and Scott M. Thompson 38. NEUROGENESIS AND EPILEPSY Jack M. Parent and Michelle M. Kron 39. Temporal Lobe Epilepsy and the BDNF Receptor, TrkB J.O. McNamara and H.E. Scharfman 40. Alterations in the Distribution of GABAA Receptors in Epilepsy Carolyn R. Houser, Nianhui Zhang, and Zechun Peng 41. GABAA receptor plasticity during status epilepticus Suchitra Joshi and Jadeep Kapur 42. Plasticity of GABAA receptors relevant to neurosteroid actions Istvan Mody 43. GABAA Receptor Plasticity in Alcohol Withdrawal Richard W. Olsen and Igor Spigelman 44. REGULATION OF GABAA RECEPTOR GENE EXPRESSION AND EPILEPSY Amy R. Brooks-Kayal, and Shelley J. Russek 46. Astrocytes and Epilepsy Jerome Clasadonte and Philip G. Haydon 45. Chloride homeostasis and GABA signaling in temporal lobe epilepsy Richard Miles , Peter Blaesse, Gilles Huberfeld , Lucia Wittner, and Kai Kaila 47. Astrocyte dysfunction in epilepsy Christian Steinhäuser, Gerald Seifert 48. Glia-neuronal interactions in ictogenesis and epileptogenesis: role of inflammatory mediators Annamaria Vezzani, Stephan Auvin, Teresa Ravizza, Eleonora Aronica 49. GLIA-NEURON INTERACTIONS: NEUROSTEROIDS AND EPILEPTOGENESIS Giuseppe Biagini, Carla Marinelli, Gabriella Panuccio, Giulia Puia, and Massimo Avoli 50. Gene Discovery in the Genetically Complex Epilepsies Ruth Ottman SECTION IV - Epilepsy genes and development 51. Strategies for Studying the Epilepsy Genome Thomas N. Ferraro, Dennis J. Dlugos, Hakon Hakonarson, Russell J. Buono 52. Sodium Channel Mutations and Epilepsy William A. Catterall 53. Potassium Channelopathies of Epilepsy Robert Brenner and Karen S. Wilcox 54. The Voltage-Gated Calcium Channel and Absence Epilepsy Jeffrey L. Noebels 55. Mutated GABAA receptor subunits in idiopathic generalized epilepsy Patrick Cossette, Pamela Lachance-Touchette, and Guy A. Rouleau 56. The GABAA?2(R43Q) mouse model of human genetic epilepsy Steven Petrou and Christopher A. Reid 57. GABAA RECEPTOR SUBUNIT MUTATIONS AND GENETIC EPILEPSIES Robert L. Macdonald, Jing-Qiong Kang, and Martin J. Gallagher 58. Nicotinic acetylcholine receptor mutations Ortrud K. Steinlein, Sunao Kaneko, and Shinichi Hirose 59. Gene Interactions and Modifiers in Epilepsy Miriam H. Meisler, and Janelle E. O'Brien 60. Rare genetic causes of lissencephaly may implicate microtubule-based transport in the pathogenesis of cortical dysplasias Judy S. Liu, Christian R. Schubert, and Christopher A. Walsh 61. The Generation of Cortical Interneurons Diego M. Gelman, Oscar Marín, and John L. R. Rubenstein 62. Genes in infantile epileptic encephalopathies Christel Depienne, Isabelle Gourfinkel-An, Stéphanie Baulac, and Eric LeGuern 63. Developing Models of Aristaless-related homeobox mutations Eric D. Marsh and Jeffrey A. Golden 64. Haploinsufficiency of STXBP1 and Ohtahara syndrome Hirotomo Saitsu, Mitsuhiro Kato, and Naomichi Matsumoto 65. mTOR and Epileptogenesis in Developmental Brain Malformations Michael Wong and Peter B. Crino 66. Major Susceptibility Genes for Common Idiopathic Epilepsies: ELP4 in Rolandic Epilepsy and BRD2 in Juvenile Myoclonic Epilepsy Deb K Pal and David A Greenberg 67. Myoclonin1/EFHC1 in cell division, neuroblast migration, synapse/dendrite formation in juvenile myoclonic epilepsy T. Grisar, B. Lakaye, L de Nijs, J. LoTurco, A. Daga , and A.V. Delgado-Escueta 68. Progressive myoclonus epilepsy of Lafora José M. Serratosa, Berge A. Minassian B, and Subramaniam Ganesh 69. Progressive myoclonus epilepsy: Unverricht-Lundborg disease and Neuronal ceroid lipofuscinoses Anna-Elina Lehesjoki and Mark Gardiner 70. GABRB3, Epilepsy, and Neurodevelopment Miyabi Tanaka, Timothy M. DeLorey, Antonio V. Delgado-Escueta, and Richard W. Olsen 71. PATHOPHYSIOLOGY OF EPILEPSY IN AUTISM SPECTRUM DISORDERS Carl E. Stafstrom, Paul J. Hagerman, and Isaac N. Pessah 72. Cognitive and Behavioral Co-Morbidities of Epilepsy Jonathan K. Kleen, Rod C. Scott, Pierre-Pascal Lenck-Santini, and Gregory L. Holmes 73. Migraine and Epilepsy-Shared Mechanisms within the Family of Episodic Disorders Michael A. Rogawski SECTION V - Epilepsy therapeutics 74. Neurobiology of Depression as a Comorbidity of Epilepsy Raman Sankar, and Andrey Mazarati 75. Calcium channel ?2? subunits in epilepsy and as targets for antiepileptic drugs Annette C Dolphin 76. Targeting SV2A for Discovery of Antiepileptic Drugs Rafal M. Kaminski, Michel Gillard, and Henrik Klitgaard 77. Neurosteroids - Endogenous Regulators of Seizure Susceptibility and Role in the Treatment of Epilepsy Doodipala Samba Reddy and Michael A. Rogawski 78. Mechanisms of Ketogenic Diet Action Susan A. Masino and Jong M. Rho 79. Deep Brain Stimulation for Epilepsy: Animal Models Kevin D. Graber and Robert S. Fisher 80. Animal Models for Evaluating Antiepileptogenesis H. Steve White 81. Strategies for antiepileptogenesis: Antiepileptic drugs versus novel approaches evaluated in post-status epilepticus models of temporal lobe epilepsy Wolfgang Löscher 82. Neonatal Seizures and Neuronal Transmembrane Ion Transport Kristopher T. Kahle and Kevin J. Staley 83. Antiepileptogenesis, Plasticity of AED Targets, Drug resistance, and Targeting the Immature Brain Heinz Beck and Yoel Yaari Jan A. Gorter and Heidrun Potschka 85. Neural Stem Cell Therapy for Temporal Lobe Epilepsy Ashok K. Shetty 86. EMBRYONIC STEM CELL THERAPY FOR INTRACTABLE EPILEPSY Janice R. Naegele, Mohan C. Vemuri, and Lorenz Studer 87. Cell Therapy Using GABAergic Neural Progenitors Stewart A. Anderson and Scott C. Baraban 88. Reversing Disorders of Neuronal Migration and Differentiation in Animal Models Jean-Bernard Manent and Joseph LoTurco 89. Gene therapy of focal onset epilepsy using adeno-associated virus vector-mediated overexpression of neuropeptide Y Francesco M. Noe', Andreas T. Sørensen, Merab Kokaia, and Annamaria Vezzani 90. Adenosine Augmentation Therapy Detlev Boison