Encyclopedia of Basic Epilepsy Research

Endophenotyping......Page 1
Editor Biography......Page 2
Introduction......Page 3
Permission Acknowledgments......Page 5
Autonomic Consequences of Seizures, Including Sudden Unexpected Death in Epilepsy......Page 6
Methods......Page 7
A Cortical Focus in Generalized Absence Epilepsy......Page 8
Circuitries......Page 10
Interaction between Various Types of Epilepsy......Page 11
Future Challenges......Page 12
Further Reading......Page 13
Background......Page 14
Methods......Page 15
Difference in GABAA IPSC Properties of GAERS and NEC Rat Neurons are Nucleus-Specific......Page 16
Effects of GHB on Excitatory and Inhibitory Synaptic Potentials Recorded in VB TC Neurons......Page 17
Acknowledgements......Page 19
Further Reading......Page 20
Introduction......Page 21
Methods......Page 22
Intracellular Activity of Cortical Neurons......Page 25
Future Goals......Page 26
Further Reading......Page 27
The Thalamocortical Network - General View......Page 28
TC neurons......Page 29
Interneurons......Page 30
Synchronized Thalamocortical Oscillations......Page 31
Pathophysiological Mechanisms of CAE......Page 32
Future Challenges......Page 33
Further Reading......Page 34
Introduction......Page 35
Background......Page 36
Contribution of Cortical and Thalamic Networks to SW Discharges......Page 37
Thalamic Networks and SW Discharge Rhythmogenesis......Page 38
Role of Cortical Networks in SW Discharge Initiation......Page 39
Mechanisms of Cortical Hyperexcitability in Absence Seizures......Page 40
Conclusions and Directions for Future Research......Page 42
Further Reading......Page 43
Background......Page 44
KA-Induced Seizures......Page 45
Future Goals......Page 46
Further Reading......Page 47
Introduction......Page 48
Introduction......Page 1457
Background......Page 49
In Vitro Electrophysiology: Susceptibility to Kainate-Induced Epileptiform Activity......Page 50
In Vitro Electrophysiology: Dentate Gating......Page 51
In Vitro Electrophysiology: Intrinsic and Synaptic Properties of Dentate Granule Cells......Page 52
Further Reading......Page 53
Introduction......Page 54
Adult Neurogenesis and Mesial Temporal Lobe Epilepsy......Page 818
Photothrombosis......Page 55
Arterial Occlusion Models......Page 56
Future Goals......Page 57
Further Reading......Page 58
Introduction......Page 59
Networks in Epilepsy......Page 60
Audiogenic Seizures......Page 61
Establishing Inferior Colliculus as the Consensus AGS Initiation Site......Page 62
Anticonvulsant Drug Action on the AGS Network......Page 63
Future Directions......Page 66
Further Reading......Page 67
Small World Characteristics are Initially Enhanced, then Transformed during Sclerosis......Page 68
Synaptic Inhibition......Page 69
Methods - AED Screening......Page 70
Calcium channels......Page 71
Synaptic Inhibition......Page 72
Potassium channels......Page 73
Future Directions and Challenges......Page 74
Further Reading......Page 75
Cognitive Effects of Seizures in Animal Models......Page 76
Electrophysiology......Page 77
GABA Transporters in Epilepsy......Page 78
Gabapentin and pregabalin......Page 80
Future Directions......Page 82
Further Reading......Page 83
Conclusion and Future Goals......Page 85
Carrier Vehicles......Page 86
Epidural Drug......Page 87
Local Perfusion by Catheter......Page 88
Acknowledgements......Page 89
Further Reading......Page 90
Pharmacology of Seizure Drugs......Page 91
ATP-Binding Cassette ABC Proteins......Page 93
RLIP76: A New Model of Multiple Drug Resistance?......Page 94
Radiolabeled Chemical Injection and Quantification......Page 96
BBB Leakage and Epilepsy: MRI Findings......Page 97
Protein Binding and pH......Page 98
Brain Edema and Drug Delivery in Epileptic Brain......Page 100
Further Reading......Page 101
Background......Page 103
Further Reading......Page 200
Enhancement of EAA Excitation......Page 860
Methods......Page 104
New Pharmacological Targets and Approaches......Page 105
Alteration of Drug Efficacy in Epileptic Animals......Page 106
Characterization of Concentration-Effect Relationships of AEDs: Pharmacokinetic and Pharmacodynamic Modeling......Page 107
Synergistic and Antagonistic Interactions of AED Combinations......Page 108
Further Reading......Page 109
Background - Drug Discovery......Page 111
Other efficacy models......Page 112
The ADD Program......Page 113
Additional Investigations......Page 114
Future Studies......Page 115
Summary......Page 116
Further Reading......Page 117
Background......Page 118
Whole-Cell Current-Clamp Recordings......Page 119
Reelin's Role in the Development of GCD......Page 213
Human Characteristics of West Syndrome/Infantile Spasms......Page 1146
Regulation of Gene Expression......Page 1458
SREDs in Hippocampal Neuronal Cultures......Page 120
Increasing Durations of SE and It's Effect on Neuronal Cell Death......Page 121
Accumulation of Glutamate or Other Metabolites into the Media do not Cause Neuronal Cell Death......Page 122
SREDs do not Cause Cell Death......Page 123
Role of Ca2+ in SE-Induced Neuronal Death......Page 124
Discussion and Future Directions......Page 125
Further Reading......Page 127
Introduction......Page 128
Transporters......Page 129
Receptors......Page 130
17beta-Estradiol......Page 541
Background......Page 131
Recent Results......Page 1427
The Postsynaptic Region......Page 132
Further Reading......Page 133
See also......Page 134
Changes in subunit composition......Page 135
Background......Page 1112
Hormones and Seizures in Animal Models of Epilepsy......Page 547
Methods and Results - Recent Advances in Structural Neuroimaging Techniques......Page 0
Refractory Status Epilepticus......Page 136
Model description......Page 1149
Findings from Bcl-w knockouts......Page 137
Other findings in experimental models......Page 138
Recent Results......Page 139
Hormones and Epilepsy......Page 140
Background-GABAA Receptor-Mediated Functions......Page 141
Sites Generating Physiological and Pathological HFOs......Page 142
Further Reading......Page 143
Introduction and Background......Page 144
Recent Results......Page 145
Combined Hippocampal-Entorhinal Cortex Slice Preparation......Page 627
Seizure-Induced Neuronal Death in the Developing Brain - Influence of Models......Page 146
Epileptic Seizure Types as Unique Diagnostic Entities......Page 1646
Methods......Page 148
Introduction and General Overview......Page 149
Epilepsy Syndromes......Page 150
Hyperpolarizing and Depolarizing GABAA Receptor-Mediated Responses......Page 347
Methods......Page 151
Pilocarpine and Lithium-Pilocarpine Models......Page 152
Kainic Acid Model......Page 153
Loss of Glutamine Synthetase and GLT-1 in Reactive Astrocytes of the Epileptic Brain: Implications for Regulation.........Page 970
Periventricular Nodular Heterotopia......Page 154
Further Reading......Page 155
Recent Findings......Page 156
Further Reading......Page 1456
Role of Interictal Discharges......Page 157
Basic Machinery of NT Release......Page 984
Occipital lobe epilepsy......Page 158
EAA system......Page 159
See also......Page 160
Further Reading......Page 161
Recent Results......Page 162
Methods......Page 163
Receptor Subtypes Involved......Page 991
Associated Variables......Page 164
Unmet Mental Health Needs......Page 165
Vagus Nerve......Page 994
Further Reading......Page 166
Methods......Page 167
Laforin and Malin Gene Function in Lafora Disease Explain a Mystery of Brain Biochemistry: Why is Glycogen Absent in Neurons?......Page 385
Treatment - Curing Lafora Disease......Page 168
What are the Most Common Designs?......Page 169
Further Reading......Page 170
Introduction......Page 172
Background......Page 173
Methodology......Page 174
Future Goals......Page 175
Further Reading......Page 176
Increases in Endogenous BDNF Reduce Vulnerability to Ischemia through Secondary Effects on NPY Gene Expression......Page 177
Mechanisms Underlying Cytokine Modulation of Neuronal Excitability (Fig. 1)......Page 649
Place cell recordings......Page 178
Long-term potentiation......Page 179
Further Reading......Page 181
Tissue from old rats......Page 629
Types of Animal Models......Page 183
Clinical Studies......Page 1566
Results......Page 184
Further Reading......Page 188
Introduction......Page 190
Background......Page 191
Results - The Unique Relationship between Autism and Epilepsy in TSC......Page 192
Further Reading......Page 194
Background......Page 196
Further Reading......Page 862
Procedures......Page 197
Bicuculline and Picrotoxin......Page 851
Huperzine A......Page 1603
Results......Page 199
Future Goals......Page 201
How is CNS Gene Delivery Accomplished? Preparation of Pegylated Immunoliposomes......Page 202
Autism in TSC......Page 203
The Role of BDNF in Epileptogenesis......Page 1035
Further Reading......Page 204
Background......Page 206
Methods......Page 207
Future Goals......Page 208
See also......Page 210
Dynorphin A......Page 1198
Introduction......Page 211
Background - Granule Cell Dispersion in Epilepsy - a Migration Defect?......Page 297
Unilateral Injection of Kainate, an Agonist of the Excitatory Transmitter Glutamate, Results in the Development of GCD in.........Page 212
Methods......Page 527
GABAA Receptor Alteration in Epilepsy......Page 300
See also......Page 216
Introduction......Page 217
Background......Page 218
Intersecting and Parallel Cell Cascades Modulate Cell Size......Page 219
Experimental Methodologies......Page 221
Recent Developments......Page 222
Experimental Setup......Page 1097
Single-Cell Microdissection for mRNA Expression Analysis in Focal Malformations......Page 223
Challenges for the Future......Page 224
Further Reading......Page 784
Further Reading......Page 1152
Effects of EB on Paired Pulse-induced Population Excitatory Postsynaptic Potentials in the Dentate Gyrus Granule Cells......Page 225
GABAA Receptor-Mediated Mechanisms and Epileptiform Synchronization......Page 314
Recent Results......Page 226
Directions for Future Research......Page 228
Further Reading......Page 229
Background......Page 230
Defense Proteins......Page 776
SPECT for Clinical Seizure Localization......Page 231
Recent Results......Page 232
Recent Results......Page 233
Future Goals......Page 234
Introduction......Page 235
Further Reading......Page 313
Developmental Aspects of Seizures......Page 806
Mutations in GABAA Receptor alpha1 Subunits......Page 236
Methods......Page 237
Extrasynaptic GABAA Receptors and Tonic Inhibition......Page 1526
See also......Page 239
Further Reading......Page 240
Background......Page 241
Voltage-Sensitive Dye Imaging......Page 589
Results......Page 242
Sex Differences in the Age-Specific Effects of GABAAergic Drugs, in Seizure-Naiumlve Rats......Page 243
Neurogenesis and the Role of Growth Factors......Page 245
Future Directions......Page 246
Dynorphin and Nociceptin/Orphanin FQ......Page 247
38......Page 248
Gene Expression in Immature and Mature Hippocampus After Status Epilepticus......Page 1103
Background......Page 899
Background......Page 298
Docosahexaenoic Acid in Synaptic and Other Neural Membranes......Page 600
Validation of Expression Data......Page 249
Recent Data......Page 250
Kindling in 30-Day Old GAERS......Page 908
Immediate-Early Genes......Page 251
Inflammation-Related Genes......Page 252
Technical Considerations......Page 254
Further Reading......Page 255
Glucose Metabolism and GABAA Receptor Dysfunction in Human Partial Epilepsy......Page 257
Role of Inflammation in Epileptogenesis and Seizure-Induced Neurodegeneration......Page 258
Classification of Seizures and Syndromes......Page 303
Results......Page 259
Work in Progress and Future Goals......Page 260
Further Reading......Page 261
Background......Page 262
Seizure Initiation and Termination......Page 605
Age-Specific Epileptogenesis......Page 263
Introduction......Page 1113
Evidence for an Endogenous Control System by the Basal Ganglia Circuits......Page 265
Future Directions-Hypothesis and Potential Targets......Page 270
Further Reading......Page 271
Models of Epileptogenesis and Transporter Proteins......Page 273
Recurrent Synaptic Actions and the Genesis of Epileptiform activity......Page 1157
Immunoblotting and Quantitative Densitometry......Page 274
Diffusion Weighted Imaging......Page 275
Further Reading......Page 276
Introduction......Page 277
Multiplicity of GABAergic Systems and Functions......Page 278
Neurotrophic Factors......Page 279
Seizure Susceptibility of CAII-Deficient Mice......Page 280
Biophysical Properties of GABA Transporters and Dynamic Equilibrium......Page 1524
Recent Results......Page 281
Further Reading......Page 282
Background......Page 284
Animals and Tissue Sample Preparation......Page 285
Abnormal cortical-subcortical interactions......Page 286
Twin Studies......Page 287
Isobaric tags for relative and absolute quantification......Page 288
Ethanol Withdrawal-Induced Convulsions......Page 289
Introduction......Page 291
Ionic Mechanism of GABAA Receptor-Mediated Inhibition......Page 292
Alterations in GABAA Receptor-Mediated Inhibition......Page 293
Cross-Over Studies......Page 1628
GABAB Receptor-Mediated Inhibition in Human Epileptogenic Cortex......Page 294
Future Goals......Page 295
Further Reading......Page 296
Methods......Page 299
Adrenocorticotrophin......Page 301
Further Reading......Page 302
The immature hippocampal network generates a primitive universal pattern......Page 304
Electrophysiological recordings of the BG circuits......Page 928
Generalization of theses features to other brain structures......Page 305
Implications for the epilepsies......Page 306
Maternal Oxytocin Reduces [Cl-]I before Delivery and Shifts Transiently GABA to Inhibition (Figure 3)......Page 307
Region-specific Effects of beta-Estradiol and Progesterone on Low Mg2plusmn-induced Epileptiform Activity......Page 308
Relevant Website......Page 309
Background......Page 310
Methods......Page 311
Future Goals......Page 312
Changes in Extracellular Glucose Levels Increase SNR GABAergic Neuron Firing......Page 789
GABAA Receptors and Epileptiform Synchronization in the Limbic System......Page 315
GABAA Receptors and Epileptiform Synchronization in Human Focal Cortical Dysplasia......Page 319
See also......Page 320
Introduction......Page 322
The Role of the Basal Ganglia Circuits in the Control of Epileptic Seizures......Page 924
CREB/ICER......Page 323
Proenkephalin and prodynorphin mRNA......Page 324
Further Reading......Page 325
Summary and Future Directions......Page 1530
Background: Mutations in GABAA Receptor Subunit Genes......Page 327
Postsurgical evaluation......Page 1697
Seizure Behaviors and Electroencephalographic (EEG) Monitoring......Page 329
Histological and Immunocytochemical (ICC) Methods......Page 330
Potential reorganization of GABAergic axons......Page 331
Conclusions and Directions for Future Research......Page 332
Animal Models of Drug-Resistant Epilepsy......Page 333
Introduction......Page 334
SE: The GABA Hypothesis......Page 335
Mechanism of GABAA Receptor-Mediated Inhibition......Page 336
See also......Page 337
Cell Counts......Page 338
Detection of DNA Fragmentation by in situ Nick Translation Histochemistry......Page 339
Background......Page 340
Recent Results......Page 342
Future Goals......Page 343
Further Reading......Page 344
Introduction......Page 346
Diversity of GABAergic Interneurons......Page 348
GABAergic Circuits Involved in Thalamocortical Spike-Wave Seizures......Page 349
Further Reading......Page 350
Introduction......Page 352
Introduction......Page 652
Methods......Page 956
Recent Results......Page 354
Relevant Website......Page 355
Background - Epileptic Syndromes Associated with Mutated Cytoskeleton Genes......Page 356
Methods - The Genotype-Phenotype Correlations in Epilepsy: A Real Way of the Cross......Page 358
What can we learn from the gene structure and the encoded protein?......Page 359
Identification of proteins by mass spectrometry......Page 1020
Distribution of the protein in various tissues......Page 360
Findings......Page 1349
Classification and Differential CNS Expression of GABA Transporters......Page 361
Future Goals......Page 362
Introduction - Non-ion Channel Genes in Human Epilepsy......Page 363
Background......Page 1268
Methods......Page 668
Complex Seizure Phenotype in Brunol4 Mutant Mice......Page 364
See also......Page 369
Further Reading......Page 370
GABAR Mutations in Human Idiopathic Generalized Epilepsy (IGE) and Angelman Syndrome (AS)......Page 371
Fundamentals of Electrical Stimulation......Page 372
Bridging the Gap Between BBB Alteration and Neuronal Hyperexcitability......Page 373
Introduction......Page 375
Genetic Linkage......Page 376
Animal Models of Epilepsy and Seizures......Page 582
Seizure-Related Acute MRI Changes......Page 680
Summary and Directions for Future Research......Page 378
Further Reading......Page 379
Methods......Page 380
Lis1......Page 381
Other lissencephaly genes and epilepsy......Page 382
Evaluation of Seizure Etiology......Page 1690
Mechanisms of the Biphasic Structural Alterations......Page 824
Further Reading......Page 384
Myoclonin/EFHC1 Gene Function in JME Explains a Contradiction in an Idiopathic Epilepsy: Why do some JME Patients have Areas of Thicker Brain Cortex?......Page 387
Genotyping Adolescent Myoclonic Epilepsy Helps Treatment Choice......Page 388
Further Reading......Page 390
Human Epilepsy as a Complex Genetic Trait: Lessons from Animal Models and Prospects for the Future......Page 392
Axon Sprouting and Increased Recurrent Excitation......Page 1295
Genes for Genetically Complex Epilepsy in Human......Page 393
Methods......Page 394
Ampakine Treatment Increase BDNF and can Restore LTP in Models of Cognitive Impairment......Page 395
Rodents with Genetically Complex Absence, or Petit-mal Seizures......Page 396
Further Reading......Page 1008
Is Mendelian Epilepsy Really all that Genetically Simple? Studying Human in Mouse......Page 398
Further Reading......Page 399
Excitotoxic Cell Death: A Common Pathologic Mechanism in Neurodegenerative Diseases......Page 400
Experimental Genetic Approach: Identification of Quantitative Trait Loci (QTLs)......Page 401
Recent Results......Page 402
Future Goals: Challenges for the Future......Page 403
Further Reading......Page 404
SCN1B......Page 405
Recent Results......Page 1012
SCN1A......Page 406
Neuronal specificity of SCN1A mutations......Page 407
Chloride Channels......Page 408
Further Reading......Page 409
C57BL/6J and DBA/2J Mice......Page 411
Monoamines......Page 412
Genetic Studies......Page 413
Pharmacological studies......Page 414
Genetic Studies: QTL Confirmation and Analysis......Page 416
Future Directions - Relevance to Human Epilepsy......Page 417
Further Reading......Page 418
ADNFLE: What is the Phenotype?......Page 419
In vivo SE Causes Increased [Ca2+]i, Altered Ca2+ Homeostasis, and a Prolonged-Elevated [Ca2+]i Plateau......Page 420
Are there Mutation-Specific Associated Features in ADNFLE?......Page 421
What Stories are Mouse and Other Models Telling?......Page 422
Relevant Websites......Page 423
Background - The Tripartite Synapse......Page 424
The Astrocytic Adenosine Cycle......Page 425
Reactive Astrocytosis Disrupts the Adenosine and Glutamine Cycles......Page 426
Directions for Future Research - Could treatments be Targeted through the Astrocyte?......Page 427
Further Reading......Page 428
Characteristics and Nomenclature of Glutamate and GABA Transporters......Page 429
Glutamate Transporters......Page 430
Future Directions......Page 432
Further Reading......Page 433
Introduction......Page 434
Introduction......Page 1025
Methods......Page 435
Recent Results......Page 437
See also......Page 439
Further Reading......Page 440
Posttraumatic Epilepsy Caused by Fluid Percussion Injury......Page 441
Methods......Page 442
Glutamate Transporters in Gliomas......Page 443
System xc Function in Gliomas......Page 444
Preclinical Studies Using Pharmacological Inhibition of System xc to Inhibit Glutamate Release......Page 446
Further Reading......Page 447
Unique Properties of Astrocytes......Page 449
Astrocyte-specific enzymes......Page 450
Contribution of Astrocyte with Altered Properties to Seizure-Inducing Mechanisms......Page 451
See also......Page 452
Further Reading......Page 453
Dysfunction of glutamate transport and synthesis......Page 454
Metabotropic glutamate receptors and astroglial Ca2+ signalling in epilepsy......Page 455
Water channels......Page 456
Tumor-associated epilepsy......Page 457
Perspectives and Future Directions......Page 458
Further Reading......Page 459
Background......Page 460
Recent Results......Page 461
Tumor Treatment-Induced Excitabiltiy Changes......Page 464
Further Reading......Page 465
Introduction......Page 467
Methods......Page 468
mGluR1/5 Contribution to Synaptic Plasticity......Page 469
mGluR1a/5 Involvement in Seizure Activity In Vitro......Page 470
See also......Page 471
Further Reading......Page 472
Background......Page 473
Methods......Page 475
Recent Results......Page 476
Future Directions......Page 478
See also......Page 479
Further Reading......Page 480
Background......Page 481
Recent Results......Page 482
Future Goals......Page 486
Further Reading......Page 487
Background......Page 488
Long-Lasting Effects of Group I mGluR Activation on Synaptic Efficacy and Network Excitability......Page 489
Epileptogenic Propensity Resulting from Selective Group I mGluR Activation......Page 490
Induction of In Vitro Epileptogenesis via Group I mGluR Activation: Key Features......Page 491
Downstream Second Messengers: Interplay of PKC Isoforms in Induction vs. Suppression of In Vitro Epileptogenesis......Page 492
Future Goals and Challenges......Page 493
Further Reading......Page 494
Physiological Role of Kainate Receptors in Glutamatergic Synaptic Transmission......Page 495
Degenerative Changes and Mossy Fiber Sprouting in the Kainate Models of TLE......Page 496
Role of Kainate Receptors Activation in Acute Seizure Generation......Page 499
Role of Kainate Receptors in Chronic Seizure Generation......Page 500
See also......Page 501
Further Reading......Page 502
Background - Functional Anatomy of the Dentate Gyrus......Page 503
Increased Neurogenesis of Dentate Granule Neurons......Page 504
Changes in the Functional Connectivity of Dentate Granule Neurons......Page 505
Changes in the Elementary Properties of Synapses and Receptors......Page 506
Collective Properties of the Dentate Gyrus in Seizure Discharge......Page 508
Further Reading......Page 509
Granule-Cell Connectivity and Plasticity......Page 510
Electrophysiological Recordings......Page 511
Kindling In Vitro......Page 512
Activation of the Mossy Fibers Provokes GABAA Receptor-Mediated Monosynaptic Responses in their Target Cells of CA3......Page 513
Functional Implications with Regard to Epilepsy......Page 515
Future Goals......Page 517
See also......Page 518
Further Reading......Page 519
Introduction......Page 520
Background......Page 521
Results......Page 522
Future Goals......Page 523
Further Reading......Page 524
Introduction......Page 525
Inclusion/Exclusion Criteria......Page 1626
Mechanisms of Ovarian Hormones for Modulation of Seizures......Page 528
Nonclassical Actions of Progestins for Antiseizure Effects......Page 529
Drug Interactions......Page 1627
Future Goals......Page 531
See also......Page 532
Further Reading......Page 591
The Emerging Role of Mitochondrial Dysfunction and Oxidative Stress in Epilepsy......Page 533
Methods......Page 534
Region-specific Effects of beta-Estradiol and Progesterone on Low Mg2plusmn-induced Epileptiform Activity (Table 1)......Page 535
Synchrony, Complexity, and Intermittency in Network Models......Page 536
Hormones and Their Action......Page 538
Genetic Associations with TLE......Page 1504
Progesterone and Related Neurosteroids......Page 540
Testosterone......Page 542
Future Challenges......Page 543
Further Reading......Page 544
Introduction......Page 546
Quantitative analysis of the mRNA content of selected genes of interest......Page 764
Progesterone - Cellular Level......Page 548
Estradiol and Progesterone - Circuit Level......Page 550
Implications for Treatment Strategies......Page 551
Further Reading......Page 552
Thyrotrophin-releasing hormone......Page 553
Further Reading......Page 1654
Adenosine......Page 1454
Properties of recurrent synapses between CA3 pyramidal cells......Page 895
General methods......Page 554
Estradiol/progesterone......Page 555
Epidemiology and clinical features......Page 1681
Methods......Page 556
Further Reading......Page 557
Background......Page 558
AR-Mediated Antiseizure Effects......Page 559
AR-Independent Antiseizure Effects......Page 560
Methods......Page 561
Summary and Future Goals......Page 562
Further Reading......Page 563
Introduction and Background......Page 565
Introduction......Page 1668
Results......Page 566
Further Reading......Page 570
Introduction......Page 572
Excitatory Amino Acid-Induced Convulsions......Page 573
Results......Page 574
Further Reading......Page 575
Development of Sex Differences in SNR-Mediated Seizure Control......Page 576
Development of Sex Differences in SNR-Mediated Seizure Control (Table 1)......Page 577
Background......Page 578
Imaging Characterization of Familial Temporal Lobe Epilepsies......Page 579
Introduction......Page 580
Progesterone, Neurosteroids and Catamenial Epilepsy......Page 583
Treatment Selection......Page 1693
Testosterone, Androgenic Neurosteroids and Seizure Susceptibility......Page 585
Directions for Future Research......Page 586
Further Reading......Page 587
Background......Page 588
Cellular Properties and Synaptic Connectivity of CA3 Pyramidal Cells: Mechanisms for Epileptic Synchronization.........Page 894
Introduction......Page 593
Background......Page 1496
Novel Designs......Page 594
Recent Results......Page 595
Future Goals......Page 596
Further Reading......Page 598
Properties of CA3 pyramidal cells......Page 599
Further Reading......Page 1144
Background and Methodological Issues......Page 1431
A’More Detailed Example: Imaging of Intrinsic Optical Signals (IIOS)......Page 601
Rationale......Page 602
Results......Page 603
Recent Results......Page 1460
See also......Page 604
Optical Monitoring of Circuitry Activity In vitro......Page 606
Icta-Interictal Relationships......Page 913
Further Reading......Page 1465
Loading Issues......Page 607
Imaging Issues......Page 608
An In Vitro Model of Surround Inhibition......Page 609
Patch-clamp Recordings......Page 610
Further Reading......Page 612
fMRI......Page 613
p35-/- Mouse......Page 1508
Puberty......Page 614
SPECT for Clinical Seizure Localization: Reading and Analysis......Page 615
Conclusions......Page 1216
Morphological changes......Page 815
Ionic currents underlying action potentials in cortical neurons......Page 616
Seizure Initiation Associated with Activation of Transient Epileptiform Events......Page 1233
See also......Page 618
Further Reading......Page 619
Introduction......Page 620
MRI of the Pilocarpine Model of Epilepsy......Page 621
Background - Problems in Studying How Seizures Stop......Page 1450
Recent Results......Page 622
T2-Weighted Imaging......Page 623
Results - Examples of the Preparation's Utility......Page 809
Tachykinins and Epilepsy......Page 625
Introduction......Page 811
Using Intrinsic Optical Signal Changes to Analyze Epileptic Activity and Seizures......Page 626
Genes, Channels, and Receptors......Page 1470
Impairment......Page 628
Further Reading......Page 630
Seizures, Epilepsy, and the Blood-Brain Barrier......Page 631
Background and Methodologies......Page 1240
Results......Page 1173
Brain Development, Vasculogenesis, and Epilepsy......Page 633
Osmotic Opening of BBB......Page 635
Recent Results......Page 636
Future Directions......Page 640
Further Reading......Page 641
Introduction......Page 642
Background......Page 643
Methods......Page 644
Future Goals......Page 645
Rapid Degeneration of the Neuronal K-Cl Cotransporter, KCC2, after Trauma......Page 646
See also......Page 647
Background......Page 1251
Inflammatory Molecules in Human Epileptogenic Tissue......Page 648
Further Reading......Page 651
Cytokines and Chemokines......Page 654
Recent Results......Page 655
Further Reading......Page 658
Microinjection Studies......Page 659
Mossy Fiber Sprouting......Page 1270
Neuroprotection Provided by Newer AEDs......Page 660
Future Goals......Page 661
Further Reading......Page 662
Introduction......Page 664
Perisomatic Inhibitory Cells......Page 665
Dendritic Inhibitory Cells......Page 666
Long-Range Interneurons......Page 667
Perisomatic Inhibition......Page 669
Dendritic Inhibition......Page 670
Directions for Future Research......Page 672
Introduction......Page 675
Further Reading......Page 674
Dentate Gyrus......Page 676
Methods......Page 677
Conclusions and Future Directions......Page 1593
Neuroimaging in Familial MTLE......Page 1701
Entorhinal Cortex......Page 678
Further Reading......Page 679
Susceptibility and Resistance of GABA Neurons to Seizure-Induced Damage......Page 681
Up-regulation of GAD mRNAs and proteins......Page 682
Alterations in remaining GABA neurons that could impair their function......Page 684
See also......Page 685
Further Reading......Page 686
Future Goals......Page 687
Experimental Studies......Page 1591
Recent Results......Page 690
Further Reading......Page 692
Future Challenges......Page 693
Na+ Channels......Page 694
BDNF and Synaptic Plasticity in Hippocampus......Page 695
HCN Channels......Page 696
Future Directions......Page 697
Further Reading......Page 698
Recent Results......Page 699
Clinical Phenotypes in the Epileptic Channelopathies......Page 700
SCN1A mutations......Page 701
KCNMA1 mutations......Page 702
Rationale......Page 703
Partial cortical deafferentation in cats......Page 704
Further Reading......Page 705
Epileptogenic Alterations in Excitable Neuronal Properties......Page 706
Mammalian cell lines......Page 708
In vivo Models......Page 709
Na+ channel mutations......Page 710
Gene mutations affecting GABA receptors or Cl- channels......Page 711
Further Reading......Page 712
New Research on Biofeedback for Seizure Control......Page 714
Methods......Page 1015
Heterologous Expression Systems......Page 716
Mutations in modulatory subunits......Page 717
Mutations influencing protein-protein interaction......Page 718
Network Phenotype......Page 719
See also......Page 720
Further Reading......Page 721
Viral Vector Approaches for Antiepileptic Gene Therapy......Page 722
Methods......Page 723
Recent Results......Page 724
Future Goals......Page 1308
Further Reading......Page 725
What are BK Channels?......Page 727
BK Channel Impact on Epilepsy......Page 728
How Do Bk Channels Increase Excitability?......Page 729
Methods......Page 730
The beta4 Knockout as a Model for BK Channel Gain-Of-Function......Page 731
Regulatory Mechanisms to Prevent BK Channels Activation......Page 732
Challenges for the Future......Page 733
Synaptic Potentiation and Inhibition after Partial Seizures......Page 734
Introduction......Page 735
Presurgical Evaluation Techniques......Page 1790
Characterization of Mutant Sodium Channels by’Expression in Xenopus Oocytes......Page 736
Recent Results......Page 737
Future Goals......Page 740
Further Reading......Page 741
Introduction......Page 743
Background......Page 744
Studies in the Human TLE Hippocampus......Page 746
Introduction......Page 747
See also......Page 748
Methods......Page 749
Indirect Actions of Ketones......Page 750
Future Goals......Page 751
See also......Page 753
Further Reading......Page 754
Diet Therapies for Epilepsy......Page 755
The Epileptic EL Mouse: A Natural Model of Human Idiopathic Generalized Epilepsy......Page 756
Influence of the KD and CR on Seizure Susceptibility in Juvenile EL Mice......Page 757
Evidence that the KD Suppresses Seizure Susceptibility through CR......Page 758
Perspectives on the Antiepileptic Mechanism of CR......Page 760
Further Reading......Page 761
Initiation of the KD......Page 762
Kv1.1-/- Mouse......Page 763
Structural and Functional Characteristics of Networks Supporting Pathological HFOs......Page 1121
Low-Glycemic Index Diet......Page 765
Further Reading......Page 768
Epileptogenesis......Page 770
Synergy by Secretory Phospholipase A2 (sPLA2) and Glutamate on Inducing Neuronal Cell Death and Sustained AA Metabolic Change......Page 771
Cyclooxygenase and Models of Epileptogenesis......Page 772
Platelet-Activating Factor......Page 773
Methods - Our Acute Rat Model......Page 1434
Immunohistochemistry......Page 775
Further Reading......Page 778
Background......Page 780
Biochemical Studies......Page 781
Intracranial Single Neuron Recordings in Freely-Moving Rats......Page 933
Deficiency in Endogenous Phosphorylation of GABAAR in Human Epilepsy......Page 782
GABAergic Deficiency and Interictal Hypometabolism......Page 783
Glucose sensing in the brain......Page 786
Methods......Page 788
Interneuronopathy......Page 1148
Future Goals......Page 790
Further Reading......Page 791
Background......Page 792
Non-EEG-Based Evidence for a Preictal Period......Page 1443
13C Nuclear Magnetic Resonance Spectroscopy......Page 793
Metabolic Activation in a Genetic Model of Idiopathic Absence Epilepsy: The GAERS......Page 794
Temporal Lobe Epilepsy: Insights from the Lithium-Pilocarpine Model......Page 795
Transport of Nutrients Between Blood and Brain......Page 796
Further Reading......Page 797
Further Reading......Page 1522
Background......Page 799
Seizures Themselves Modify the Expression of Galanin and Galanin Receptors in the Brain......Page 1214
Lipid Peroxidation......Page 800
Verification in SOD Transgenic/Knockout Mice......Page 801
Mitochondrial Dysfunction and Neuronal Excitability......Page 802
Therapeutic Implications and Future Challenges......Page 803
Further Reading......Page 804
Characterization of Intrinsic Neuronal Behavior......Page 807
Genetics......Page 1150
Discovery of Kindling......Page 812
Characteristics and Mechanisms of Kindling......Page 564
Differential CNS distribution of GAT isoforms......Page 1532
Methods......Page 1534
Neural circuitry......Page 813
Pros and cons......Page 814
Conclusions and Future Goals......Page 816
Further Reading......Page 817
A’Purely Structural Model......Page 819
Background and Methods......Page 1476
Implementation of Sclerosis......Page 821
Dissociating the Tonic (Sustained) Components of REM and NREM Sleep......Page 1478
Topological Assessment of the Structural Network......Page 822
The Dentate Gyrus is a Small World Network......Page 823
Network Activity Mirrors the Biphasic Structural Alterations......Page 825
Activity in Networks with Sprouting but No Cell Loss......Page 827
Conclusions and Future Directions......Page 828
Further Reading......Page 1176
Further Reading......Page 829
Methods......Page 830
Results......Page 831
Further Reading......Page 833
Introduction - Intracellular [Cl-] Homeostasis......Page 835
Introduction......Page 1250
Experimental and Methodological Details......Page 836
Recent Results......Page 837
Computer Analysis......Page 997
Current Problems and Future Challenges......Page 839
Further Reading......Page 840
Introduction......Page 841
Clinical Epilepsy, What to Model......Page 842
Acute Experimentally-Induced Seizure Models......Page 845
Uses of Experimental Animal Models......Page 846
Understanding Fundamental Neuronal Mechanisms......Page 847
See also......Page 848
Further Reading......Page 849
Background......Page 850
Drugs Affecting GABAA Receptors......Page 852
How to Better Analyze Local Synaptic Circuits During Epileptogenesis?......Page 853
See also......Page 854
Further Reading......Page 855
Introduction and Background......Page 856
Suppression of GABAergic Inhibition......Page 857
Future Goals......Page 861
Features of Seizure-like Events......Page 863
Methods......Page 864
Low Ca Induced Epileptiform Activity......Page 865
Low Mg Induces Seizure-like Events......Page 866
Stimulation Induced Seizures......Page 867
Further Reading......Page 868
Predisposition......Page 870
Relation of Forebrain and Brainstem Seizures to Human Seizures......Page 871
Generalized Convulsive Seizures......Page 872
Seizure Expression......Page 873
Predisposition Model for Preclinical Development of Treatments and Preventions......Page 874
See also......Page 875
Further Reading......Page 876
Introduction: Rationale for the Model......Page 877
Methods: Generation of the Model......Page 878
Response to AEDs and the Usefulness in Screening Tests......Page 880
Neuropathology......Page 881
Further Reading......Page 882
Practical Methodological Issues......Page 883
Cellular Mechanisms......Page 884
Further Reading......Page 886
Cell Culture Methods......Page 887
Physiology and pharmacology of inhibitory synapses......Page 888
Synaptic Plasticity......Page 889
Excitotoxicity......Page 890
Effect of Noradrenergic Augmentation......Page 891
Summary and Directions for Future Research......Page 892
Further Reading......Page 893
Developmental Changes in GABAA Signaling......Page 896
Further Reading......Page 897
The Development of Network Activity......Page 900
Generation and Spread of Activity......Page 901
The Ideal Animal Model of Infantile Spasms......Page 902
Methods Used for Studies of Activation of Gene Expression......Page 904
Background......Page 906
Kindling in Adult GAERS and WAG/Rij Animals......Page 907
Future Goals......Page 909
Further Reading......Page 910
Background......Page 912
The Role of Perirhinal Cortext in Limbic Seizure Propagation......Page 916
Background......Page 917
Future Goals......Page 919
Recent Results......Page 921
Background......Page 922
Recent Results......Page 1160
Introduction......Page 925
Early Evidence of a Gating System for the Control of Epileptic Seizures......Page 926
Role of the Different BG Pathways in the Control of Seizures (see Figure 1)......Page 927
Synchrony and the Unbinding Problem......Page 1095
Depolarization-induced suppression of inhibition (DSI) by endocannabinoids......Page 1206
Role of the dopaminergic neurotransmission......Page 929
Seizure Models in our Studies......Page 1227
Further Reading......Page 930
99......Page 931
Background......Page 932
A’Prospect for Galanin-Based Antiepileptic Drugs......Page 1115
Early-Life Seizures Increase Vulnerability to Later Life Seizure-Induced Injury......Page 934
Kainic Acid and Opioid Peptides......Page 1221
Substance P and SE......Page 1235
GABAA Receptor Changes Early in Life......Page 935
Future Directions......Page 937
Further Reading......Page 938
Introduction......Page 940
Aberrant Neurogenesis in mTLE......Page 941
Methodological Approaches......Page 942
Background......Page 943
Further Reading......Page 944
Introduction......Page 946
Methods......Page 947
Future Goals......Page 948
Further Reading......Page 950
Recent Results......Page 951
Background......Page 834
Future Goals......Page 952
Further Reading......Page 953
Background......Page 955
Drug Resistance in Chronic Epilepsy: The Transporter Hypothesis......Page 1258
Future Goals......Page 957
See also......Page 958
Further Reading......Page 959
Introduction......Page 960
Background......Page 961
Results......Page 962
Directions for Future Research......Page 964
Further Reading......Page 966
Introduction......Page 967
Regulation of Hippocampal Inhibitory Synaptic Transmission by the Astrocytic Glutamate-Glutamine Cycle......Page 968
Further Reading......Page 971
Dopamine Innervation of Prefrontal Cortex......Page 973
Methods......Page 974
Future Directions......Page 975
Further Reading......Page 978
Background......Page 979
Recent Results......Page 980
Future Directions......Page 982
Further Reading......Page 983
Munc13......Page 985
Kindling......Page 986
Neuroprotection......Page 1211
Background......Page 1589
Asymmetric Accumulation of SNARE Complexes......Page 987
Effects of Levetiracetam......Page 988
Further Reading......Page 989
Background and Recent Results......Page 990
Effect of Noradrenergic Deficits......Page 992
Localization of Noradrenergic Anticonvulsant Effect......Page 993
Further Reading......Page 995
Background......Page 996
Downregulation of AA-I nositol Lipid Signaling and Resistance to Seizures......Page 1282
Results......Page 998
Further Reading......Page 1000
Background - BDNF Facilitates Synaptic Plasticity in Adult Brain......Page 1001
Methods......Page 1002
Role in Epilepsy Surgery......Page 1003
Ampakine Regulation of BDNF Expression in vitro and in vivo......Page 1004
Future Goals......Page 1007
Fibroblast Growth Factor-2......Page 1009
Proliferation and differentiation......Page 1010
Gene Expression Studies......Page 1011
Further Reading......Page 1014
GDNF: A Neurotrophic Factor Against Epilepsy......Page 1775
Recent Results......Page 1017
Further Reading......Page 1018
Neurotrophic Factors and Neuroprotection......Page 1019
Challenges for the Future......Page 1296
Methods......Page 1021
Directions for Future Research......Page 1022
Further Reading......Page 1024
The Focus upon Neuroactive Peptides......Page 1026
Effects of BDNF on Synaptic Transmission......Page 1027
Role of BDNF in Animal Models of Epilepsy......Page 1028
See also......Page 1029
Further Reading......Page 1030
Multidrug Resistance......Page 1031
Neurotrophins, their Receptors, and Distribution within Hippocampus......Page 1032
Methods......Page 1033
Additional Studies from Other Laboratories......Page 1034
See also......Page 1036
Further Reading......Page 1037
Introduction......Page 1038
Background......Page 1039
Recent Results......Page 1040
See also......Page 1042
Further Reading......Page 1043
Introduction......Page 1044
Cation-Dependent Chloride Cotransport......Page 1045
Effects of Osmolarity and Cell Volume Changes on Neuronal Ion Channels......Page 1046
Volume changes regulating phosphorylation and activity of ion cotransporters......Page 1047
Variability in Occurrence of Peri-Ictal Imaging Changes......Page 1739
Results......Page 1048
Future Goals......Page 1049
Further Reading......Page 1050
Background......Page 1052
Methods......Page 1053
Results......Page 1054
See also......Page 1056
Further Reading......Page 1057
Background......Page 1058
Methods......Page 1059
Changes in Extracellular Potassium Concentration......Page 1060
Changes in Extracellular Calcium Concentration......Page 1062
Further Reading......Page 1063
Introduction......Page 1065
Elevated Interstitial Potassium......Page 1066
Low Calcium......Page 1067
Cell Swelling......Page 1068
Computer Simulation of Ion Currents that Generate Seizures......Page 1069
Simulated Elevation of Interstitial Potassium......Page 1070
Seizures Promoted by [Ca2+]-Sensitive Nonspecific Cation Current......Page 1072
Conclusions and Challenges......Page 1073
Further Reading......Page 1074
Electrotonic Coupling Through Gap Junctions......Page 1075
Reactive Sprouting After Axonal Injury......Page 1361
Methods......Page 1076
Fast Oscillations at Seizure Onset......Page 1077
Challenges for the Future......Page 1078
Further Reading......Page 1079
Introduction......Page 1080
Aquaporins in the Central Nervous System......Page 1081
Nonsynaptic Mechanisms of Neuroexcitation......Page 1082
AQP4 Modulates Neuroexcitation......Page 1083
AQP4 Modulates Ion Fluxes in Seizures......Page 1084
Future Goals......Page 1085
See also......Page 1086
Further Reading......Page 1087
Background......Page 1088
ECoG Recordings in GAERS and NER......Page 1089
Effects of Carbenoxolone Administration in vivo in GAERS and NER......Page 1090
Effects of gap junction blockers......Page 1091
Conclusions and Future Goals......Page 1092
Further Reading......Page 1093
Subcellular oscillations......Page 1094
p35-/- mice......Page 1510
Death is Mainly a Parasympathetic Phenomenon that Resembles Asphyxia......Page 1436
Coupled Oscillators Modeling......Page 1096
Transitions, Noise, and Intermittency in Coupled Oscillator Models......Page 1098
Autonomous Neurodynamics, Environment, and Embodiment......Page 1101
Further Reading......Page 1102
Genetic Manipulations with Galanin and its Receptors Modify Seizure Phenotype......Page 1215
Methods......Page 1104
Recent Results......Page 1105
Further Reading......Page 1111
Methodological Approaches......Page 1114
Cellular Mechanisms of Synchronization......Page 1116
Further Reading......Page 1117
Introduction......Page 1119
Background......Page 1120
Neuronal Correlates of Ripples and FR......Page 1123
Future Goals......Page 1124
See also......Page 1217
Introduction and Background......Page 1125
Introduction......Page 1126
Persistent Increase of [Cl-]I in the Mirror Focus......Page 1128
Future Goals......Page 1129
Further Reading......Page 1130
Altered GABAA Receptor Subunit Composition in Temporal Lobe Epilepsy......Page 1131
Methods......Page 1134
Recent Results......Page 1135
Seizures and Stress Can Modify the Biological Age: Lessons from GABAA Receptors......Page 1136
Future Goals......Page 1138
Further Reading......Page 1139
Introduction......Page 1140
Results......Page 1141
Future Goals......Page 1143
Animal Models of Infant-Onset Epileptic Encephalopathy......Page 1145
Concepts of Pathogenesis......Page 1147
Brainstem dysfunction......Page 785
Conclusions and Future Directions......Page 1151
Galanin Modulation of EpileptogenicityPeptides......Page 1153
Overview of Models and Techniques......Page 1154
Seizures and the Developing Brain......Page 1155
Future Directions......Page 1156
Introduction......Page 1158
Background......Page 1159
See also......Page 1162
Background......Page 1164
Methods......Page 1165
Opioids and cannabinoids - convulsant or anticonvulsant?......Page 1209
Recent Results......Page 1166
Further Reading......Page 1167
Brain Mechanisms Linking Epilepsy to Sleep......Page 1168
Focal Over Expression of Galanin in the Brain Suppresses Seizures......Page 1169
See also......Page 1170
Further Reading......Page 1171
Background......Page 1172
Future Goals......Page 1175
Introduction......Page 1177
Brain Imaging of P-glycoprotein Function in Drug-Resistant Epilepsy......Page 945
Background......Page 1178
Methods......Page 1179
Recent Results......Page 1180
Further Reading......Page 1183
Action of AEDs on PTZ-Induced Convulsions......Page 1184
Bone Health......Page 1186
New Developments of fMRI in Epilepsy Patients......Page 1187
Behavioral Testing......Page 1188
Direct Current Membrane Polarization......Page 1561
Endogenous Neuroprotection and the Two Hit Phenomen May Share Common Mechanisms......Page 1189
Introduction......Page 1190
Recent Knowledge of Cannabinoid Action......Page 1191
Methods......Page 1192
Results......Page 1193
Future Goals......Page 1195
Further Reading......Page 1197
Receptors......Page 1199
Overview......Page 1498
Alterations in the N/OFQ-NOP System in Response to Seizures......Page 1200
Etiology of Status Epilepticus......Page 1660
Future Goals......Page 1201
Further Reading......Page 1202
Introduction......Page 1203
Endogenous Opioid and Cannabinoid Systems-Basic Properties......Page 1204
Interneurons......Page 1205
Cellular studies......Page 1207
Seizures affect endocannabinoids......Page 1210
See also......Page 1212
Methods......Page 1213
Effects of Opioid Agonists and Antagonists on Seizure Activity......Page 1218
Glutamate Transporter Subtypes......Page 1219
Kindling and Opioid Peptides......Page 1220
Antiepileptogenesis and Opioid Receptors......Page 1222
GluTs Control Early Network Activity: Their Inhibition Results in Slow Network Oscillations In Vitro......Page 1519
Further Reading......Page 1224
Opioid Systems Involved in Seizures......Page 1226
GABA system......Page 1228
Other Changes in the Opioid Systems of Morphine-exposed Animals that Might Account for Changes in Seizure Susceptibility......Page 1229
Conclusion and Future Directions......Page 1230
Further Reading......Page 1231
Tachykinins and their receptors......Page 1232
CNS effects......Page 1234
Neurokinin B and SE......Page 1236
SP in Human Epilepsy......Page 1237
Further Reading......Page 1238
Introduction......Page 1239
Glutamate Metabolism......Page 1541
Phenytoin-Resistant Kindled Rats......Page 1241
Post-Status Epilepticus Models of TLE......Page 1243
Further Reading......Page 1244
Background and Methods......Page 1245
Background......Page 1246
Further Reading......Page 1248
Effects of Tiagabine on Neurons in Human Epileptogenic Tissue......Page 1252
Future Goals......Page 1254
Further Reading......Page 1255
Mechanisms of Pharmcoresistance......Page 1256
The Development of Tolerance......Page 1257
Drug Resistance in Chronic Epilepsy: The Target Hypothesis......Page 1259
See also......Page 1260
Further Reading......Page 1261
Axon Sprouting in Epilepsy......Page 1262
Methods......Page 1264
Results......Page 1265
See also......Page 1266
Further Reading......Page 1267
Methods and Experimental Approach......Page 1269
Synaptic Reorganization in CA1 and Subiculum......Page 1272
Hyperexcitability and Metabolic Imaging......Page 1729
Further Reading......Page 1274
Background......Page 1275
Methods - Experimental Approaches to the Study of Dendritic Abnormalities......Page 1276
Results - The Impact of Seizures on Developing Dendrites......Page 1277
Challenges for the Future......Page 1278
Further Reading......Page 1279
Introduction......Page 1280
Rapid Kindling Epileptogenesis......Page 1281
Diacylglycerol Kinase Epsilon Deficiency Upregulates COX-2......Page 1284
Future Goals......Page 1285
Further Reading......Page 1286
Introduction and Background......Page 1287
Induction Methods (LTP vs. Kindling)......Page 1288
Epilepsy Animal Models......Page 1289
Further Reading......Page 1290
Definition of Epileptogenesis......Page 1292
Loss of GABAergic Interneurons......Page 1293
Future Goals......Page 1294
Further Reading......Page 1297
Gel-based procedures......Page 1298
Proteomic Analyses of Alterations of Synaptosomal Protein Complements in Control and Kindled Rat Hippocampi......Page 1299
Studies of Synaptosomal 14-3-3 Proteins......Page 1300
Alterations of the CaM System in Epileptogenesis......Page 1301
Future Goals......Page 1302
Further Reading......Page 1303
Motor Map Alterations......Page 1304
Mechanisms......Page 1306
Further Reading......Page 1307
Dendritic Spine Changes in Human Epilepsy......Page 1309
Methods......Page 1310
Focal 4-Aminopyridine Neocortical Seizures Increase Risk of Dendritic Injury under Limited Conditions......Page 1311
Secondary Generalized Kainate Seizures Cause Robust Dendritic Injury......Page 1312
Acute Seizure-Induced Dendritic Injury May Be Mediated by Calcineurin-Dependent Activation of Cofilin and Depolymerization.........Page 1313
Further Reading......Page 1314
Background......Page 1315
Methods......Page 1316
Multisynaptic Alterations of Entorhinal-Hippocampal Circuit after Kainic Acid SE......Page 1317
Future Goals......Page 1319
Further Reading......Page 1321
Introduction......Page 1322
Failed Attempts to Block MFS......Page 1323
Results......Page 1324
Further Reading......Page 1326
Introduction......Page 1328
Background......Page 1329
In vitro SE Causes Increased [Ca2+]i......Page 1330
Interpretation of Alterations in 31P Metabolism in Epilepsy......Page 1331
Alterations in Ca2+ Following Stroke-Induced AE......Page 1333
TBI-Induced Increases in [Ca2+]i Levels and Ca2+ Homeostatic Mechanisms......Page 1334
Further Reading......Page 1336
Background......Page 1337
Results......Page 1338
Further Reading......Page 1340
Introduction......Page 1341
Methods......Page 1342
Recent Results......Page 1343
Conclusions......Page 1345
Further Reading......Page 1346
Introduction......Page 1347
Hypothesis of action......Page 1348
Findings......Page 1351
Findings......Page 1352
Hypothesis of action......Page 1353
PTE in juvenile rats......Page 1354
Further Reading......Page 1355
Fundamental Elements of TBI......Page 1357
Denervation......Page 1358
Slice Culture Preparation and Schaffer Collateral Transection......Page 1359
Homeostatic Plasticity After Denervation......Page 1362
Further Reading......Page 1365
Introduction......Page 1366
Initial Studies on Iron-Induced Epileptogenesis......Page 1367
Histopathology......Page 1368
Further Reading......Page 1369
Introduction......Page 1371
Analysis of Flow......Page 1373
Hippocampal Gamma Waves Are Associated with Postictal Behavioral Alterations......Page 1374
Future Goals......Page 1375
Further Reading......Page 1376
Clinical Manifestations of Anxiety in TLE......Page 1377
Effects of kindling on interictal anxiety......Page 1378
Methods......Page 1379
Long-Term Amygdala Kindling and Interictal Anxiety......Page 1380
Receptor binding studies......Page 1381
Neurogenesis and interictal anxiety......Page 1382
Discovery of More Effective Anticonvulsant Treatments......Page 1383
Further Reading......Page 1384
Introduction......Page 1385
Emotional Disturbances......Page 1386
Effects on Cognitive Learning......Page 1387
Skilled forelimb behavior......Page 1388
Learning and Memory......Page 1389
Conclusions and Future Directions......Page 1390
Further Reading......Page 1391
Epilepsy and Depression Comorbidity......Page 1392
Animal Models of Epilepsy and Depression Comorbidity......Page 1393
Seizure-Related Mortality in Rats Bred for Depression-like Phenotypes......Page 1394
Treatments for Epilepsy and Depression Comorbidity......Page 1396
Further Reading......Page 1397
Introduction......Page 1398
Molecular Biology of Sodium Channels......Page 1399
Potassium Channels......Page 1400
KCNQ Channels in Human Neocortical Neurons......Page 1401
Future Goals......Page 1402
Acknowledgements......Page 1403
Further Reading......Page 1404
Background - Control of Intrinsic Excitability in Hippocampal Pyramidal Cells......Page 1405
Plasticity of Intrinsic Excitability in Chronic Models of Epileptogenesis......Page 1407
How Changes in Intrinsic Excitability Contribute to Epileptogenesis......Page 1408
Future Directions......Page 1409
Further Reading......Page 1410
Introduction......Page 1411
Methods......Page 1412
Spike frequency modulation......Page 1413
Synaptic Circuitry and Synchronization: Recurrent and Feedforward Circuitry......Page 1414
Adrenergic (alpha and beta) modulation......Page 1415
Summary - Directions for Future Research......Page 1416
Further Reading......Page 1417
Introduction......Page 1418
Background......Page 1419
GABA Receptors......Page 1420
Challenges for the Future......Page 1422
Further Reading......Page 1423
Introduction......Page 1424
Methods......Page 1425
Further Reading......Page 1430
Introduction - Seizures Cause Autonomic Disturbances......Page 1432
Animal Studies of Autonomic Nervous System Dysfunction During Seizures......Page 1433
Findings Using Our Model......Page 1435
Further Reading......Page 1437
Introduction......Page 1438
Background......Page 1439
Recent Results......Page 1441
Further Reading......Page 1442
EEG-Based Evidence for a Preictal State - Recent Approaches......Page 1444
Effect of AEDs on Reproductive Endocrine Dysfunction in Men......Page 1445
Recent Results......Page 1447
Conclusions and Future Directions......Page 1521
Further Reading......Page 1448
Relevant Websites......Page 1449
Methods......Page 1451
Cellular Mechanisms......Page 1452
Changes in pH and Seizure Termination......Page 1453
Endocannabinoids and Seizures......Page 1455
Global analysis of gene expression......Page 1459
Neurotransmitter Receptors, Transporters and Ion Channels......Page 1463
Future Goals......Page 1464
183......Page 1466
The Clinical Problem and Questions from the Bedside......Page 1468
Sleep Mechanisms......Page 1469
GluTs Prevent the Generation of Seizures in Rat Pups in vivo Inhibition of GluTs Leads to a 'Suppression Burst Pattern......Page 1520
Epileptogenic Sleep-Related Slow Oscillations......Page 1471
Conclusions and Challenges......Page 1473
Further Reading......Page 1474
Animal Models......Page 1477
Amygdala Kindled Kittens ESES and Landau-Kleffner Syndrome......Page 1481
Further Reading......Page 1482
Neuronal Mechanisms of the Slow Oscillation......Page 1483
Glial Mechanisms of the Slow Oscillation......Page 1484
Results - Transition from Sleep to Seizures......Page 1486
Further Reading......Page 1490
Background......Page 1491
Methods......Page 1492
Studies in Animal Models of Epilepsy......Page 1493
Further Reading......Page 1495
The Microarray Experiment......Page 1497
Microarray Analyses in Human Specimens......Page 1499
Animal Models of TLE......Page 1500
Comparison of Experimental and Human Data......Page 1501
Further Reading......Page 1502
Introduction......Page 1503
Methods......Page 1505
Future Goals......Page 1506
Further Reading......Page 1507
Electron Microscopy and EM-ICC......Page 1509
Kv1.1 knockout......Page 1512
See also......Page 1514
Further Reading......Page 1515
Introduction......Page 1516
Mechanism of Uptake......Page 1517
GluTs and Epilepsy......Page 1518
GABA Transporter Subtypes......Page 1523
GABA Transporters and Tonic Inhibition......Page 1528
Further Reading......Page 1531
Insights from recent crystal structures......Page 1535
Constitutive transporter trafficking......Page 1537
Regulated transporter trafficking......Page 1538
Future Directions and Challenges......Page 1539
Further Reading......Page 1540
Currents Associated with EAATs......Page 1542
Pharmacology and Protein Structure......Page 1545
Cellular Trafficking of Transporters......Page 1546
See also......Page 1547
Further Reading......Page 1548
Introduction......Page 1549
Methods......Page 1551
Results......Page 1552
Further Reading......Page 1553
Background - Developmental and Trauma-Induced Changes in Neuronal [Cl-] Homeostasis......Page 1554
Results......Page 1555
Future Goals......Page 1558
Further Reading......Page 1559
Introduction......Page 1560
Effect of LFS on neural excitability in animal models......Page 1562
HFS of the CNS......Page 1563
See also......Page 1564
Further Reading......Page 1565
Vagus and Trigeminal Nerve Stimulation......Page 1567
Methods......Page 1568
Effect of Preemptive LFSWS and in Fully Kindled Animals......Page 1569
See also......Page 1570
Further Reading......Page 1571
Introduction......Page 1572
Targets and Frequencies......Page 1573
Methodological Considerations and Recent Results......Page 1574
Further Reading......Page 1575
Background......Page 1577
Methods......Page 1578
Recent Results......Page 1733
Further Reading......Page 1581
Scope of the Problem......Page 1582
Background......Page 1583
Methods and Recent Results......Page 1584
Future Plans......Page 1586
Further Reading......Page 1587
Relevant Websites......Page 1588
Methods - Gene Delivery to the CNS......Page 1590
Further Reading......Page 1594
Ginseng and Other Herbal Treatments for Epilepsy......Page 1595
Methods......Page 1596
Recent Results......Page 1597
Herbal Therapies for Epilepsy......Page 1600
Introduction......Page 1601
Methodological Approaches......Page 1602
Further Reading......Page 1605
Lafora's Progressive Myoclonic Epilepsy as a Candidate for Gene Therapy......Page 1606
Studies on Pegylated Immunoliposome Delivery to Brain......Page 1607
Methodological Approaches and Results to Date......Page 1609
Electron Microscopic Confirmation of Laforin-PIL Preparations......Page 1610
Further Reading......Page 1611
Cortex Reconstructions and Fractal Dimension......Page 1613
Methods......Page 1614
Recent Results......Page 1617
Further Reading......Page 1711
Future Goals......Page 1618
Further Reading......Page 1620
The Untoward Consequences of Variable In Vivo Tropism......Page 1621
The Potential Impact of Pre-Existing Immunity and Seizure Pathology on Anti-Seizure Gene Therapy......Page 1622
Recent Results......Page 1623
Further Reading......Page 1625
Parallel-Group Studies......Page 1629
Phase III Trials......Page 1630
Monotherapy Trials......Page 1631
Presurgical Studies......Page 1632
Further Reading......Page 1633
Reproductive Endocrine Dysfunction......Page 1635
Effects of AEDs on Reproductive Endocrine Dysfunction in Women......Page 1636
Menopause......Page 1638
Conclusion - Current State of the Field......Page 1639
Further Reading......Page 1640
Introduction......Page 1641
1981 ILAE Classification of Epileptic Seizures......Page 1642
1989 ILAE Classification of the Epilepsies, Epileptic Syndromes, and Related Disorders......Page 1643
Recent ILAE Efforts to Evaluate and Revise the International Classifications......Page 1645
Need for Basic Research......Page 1648
See also......Page 1649
Further Reading......Page 1650
Background......Page 1651
Definitions and Classifications of Status Epilepticus......Page 1655
Incidence and Frequency of Status Epilepticus......Page 1657
Epidemiological Studies of Incidence......Page 1658
Directions for Future Research......Page 1661
Further Reading......Page 1662
Introduction and Background......Page 1663
Problems in Clinical Genetic Assessments......Page 1664
Single Cases and Case Series......Page 1665
Recent Results......Page 1666
Further Reading......Page 1667
Methodological Approaches and Results to Date......Page 1669
Mendelian Epilepsy Genes......Page 1671
Genetically Complex Epilepsies......Page 1675
Further Reading......Page 1676
Introduction......Page 1677
Definition and histopathology......Page 1678
Definition and histopathology......Page 1682
Polymicrogyria Phenotypes......Page 1683
Methods......Page 1684
Future Directions......Page 1685
Further Reading......Page 1686
Introduction......Page 1687
Normal FMZ binding pattern......Page 1688
Normal AMT uptake pattern......Page 1689
Evaluation of Seizure Pathology......Page 1691
Prediction of Seizure Intractability......Page 1694
11C-Flumazenil PET Scan (FMZ PET)......Page 1695
Secondary epileptic foci......Page 1696
Further Reading......Page 1698
Mesial Temporal Lobe Epilepsy......Page 1700
Familial MTLE......Page 1702
Familial TLE with Auditory Auras......Page 1703
Familial MTLE......Page 1704
Further Reading......Page 1705
Multichannel Coils and Parallel Imaging......Page 1707
Voxel-Based Morphometry......Page 1708
fMRI of Cognitive Functions......Page 1710
1H NMR Spectroscopy and Spectroscopic Imaging......Page 1713
Methods......Page 1714
1H Spectroscopy and Temporal Lobe Epilepsy......Page 1715
Interpretation of Decreased NAA levels......Page 1716
Factors Affecting the Interpretation of 31P Data......Page 1718
Glutamate and GABA: Intracellular Alterations in Neurotransmitters......Page 1719
Further Reading......Page 1721
Background/Methodologic Issues......Page 1723
Recent Results of Potential Clinical and Physiologic Importance......Page 1724
Challenges for the Future......Page 1726
Further Reading......Page 1727
Methods......Page 1728
Neuropsychologic Performance and Metabolic Imaging......Page 1730
Summary and Directions for Future Research......Page 1731
Further Reading......Page 1732
MRI Techniques......Page 1734
Abnormalities of Blood Flow and Perfusion......Page 1735
Diencephalic and Cerebellar Diaschesis......Page 1736
Lesions of the Splenium of the Corpus Callosum......Page 1737
Further Reading......Page 1740
Computed Tomography......Page 1741
Imaging Indications......Page 1742
Improving Dimensionality: Volumetric MRI......Page 1743
Decreasing Artifact: The PROPELLER Technique......Page 1744
Further Applications: The Neuroimaging of Tuberous Sclerosis......Page 1745
Further Reading......Page 1746
The Biological and Physical Basis of Diffusion Based Imaging......Page 1747
Tractography Algorithms......Page 1748
Memory - The Parahippocampal Gyrus......Page 1749
Future Goals......Page 1751
Further Reading......Page 1753
LEAT and Epileptogenesis......Page 1754
Gangliogliomas......Page 1755
Grading......Page 1757
Differential diagnosis......Page 1758
Future Goals......Page 1759
Further Reading......Page 1760
Introduction and Background......Page 1761
How Do Malformations Develop?......Page 1762
Why, in the Majority of Cases, do these MCDs Generate Epilepsy? Do the Different Types of Malformations Employ the Same.........Page 1765
Further Reading......Page 1766
Why Detect Epileptic Seizures?......Page 1768
Seizure Detection and Prediction......Page 1767
Seizure Detection Methods......Page 1769
Validation......Page 1772
Seizure Prediction Methods and Performance......Page 1773
Further Reading......Page 1774
Introduction......Page 1776
Matching Pursuit and Gabor Atom Density......Page 1777
Multichannel Analysis of the Flow of Brain.Activity......Page 1778
Seizure Propagation......Page 1779
Future Applications......Page 1782
Further Reading......Page 1783
Background......Page 1784
Tissue Studies......Page 1785
Population Genetic Association Studies......Page 1787
Acknowledgements......Page 1788
Further Reading......Page 1789
Undercutting......Page 1791
Newer Integrative and Pre- and Intraoperative Approaches for Tailored Surgical Interventions......Page 1792
Further Reading......Page 1794