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, Josee 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 Pitkanen and Tamuna Bolkvadze ; 26. Fever, febrile seizures and epileptogenesis ; Celine M. Dube, 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 Steinhauser, 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 Marin, and John L. R. Rubenstein ; 62. Genes in infantile epileptic encephalopathies ; Christel Depienne, Isabelle Gourfinkel-An, Stephanie 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 ; Jose 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 Loscher ; 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. Sorensen, Merab Kokaia, and Annamaria Vezzani ; 90. Adenosine Augmentation Therapy ; Detlev Boison