Models of Seizures and Epilepsy

An understanding of mechanisms underlying seizure disorders depends critically on the insights provided by model systems. In particular with the development of cellular, molecular, and genetic investigative tools, there has been an explosion of basic epilepsy research. Models of Seizures and Epilepsy brings together, for the first time in 30 years, an overview of the most widely-used models of seizures and epilepsy.

Chapters cover a broad range of experimental approaches (from in vitro to whole animal preparations), a variety of epileptiform phenomenology (including burst discharges and seizures), and suggestions for model characterization and validation, such as electrographic, morphologic, pharmacologic, and behavioral features. Experts in the field provide not only technical reviews of these models but also conceptual critiques - commenting on the strengths and limitations of these models, their relationship to clinical phenomenology, and their value in developing a better understanding and treatments.

Models of Seizures and Epilepsy is a valuable, practical reference for investigators who are searching for the most appropriate laboratory models for addressing key questions in the field. It also provides an important background for physicians, fellows, and students, offering insight into the potential for advances in epilepsy research.

• The first comprehensive description of animal models of epilepsy since the early 1970's
• Comprehensive analysis of "What the models model" to guide the selection of each model, and what specific questions it will answer
• Elegant examples of the use of novel technologies that can be applied in experimental epilepsy research
• World expert opinions on the clinical relevance of each model

Neurologists, epileptologists, developmental neuroscientists, medical geneticists, molecular/developmental biologists.

Contributing Authors

Foreword

Preface

1. What Should Be Modeled?

A. In Vitro Preparations

2. Single Nerve Cells Acutely Dissociated from Animal and Human Brains for Studies of Epilepsy

3. Cell Culture Models for Studying Epilepsy

4. An Overview of In Vitro Seizure Models in Acute and Organotypic Slices

5. The Use of Brain Slice Cultures for the Study of Epilepsy

6. Hippocampal Slices: Designing and Interpreting Studies in Epilepsy Research

7. Thalamic, Thalamocortical and Corticocortical Models of Epilepsy with an Emphasis on Absence Seizures

8. Studying Epilepsy in the Human Brain In Vitro

9. In Vitro Isolated Guinea Pig Brain

B. Induced Seizures in Intact Animals

10. Pharmacologic Models of Generalized Absence Seizures in Rodents

11. Models of Chemically-Induced Acute Seizures

12. Electrical Stimulation-Induced Models of Seizures

13. Alcohol Withdrawal Seizures

14. Alumina Gel Injection Models of Epilepsy in Monkeys

C. Genetic Models

15. Modeling Epilepsy and Seizures in Developing Zebrafish Larvae

16. Transgenic and Gene Replacement Models of Epilepsy: Targeting Ion Channel and Neurotransmission Pathways in Mice

17. Spontaneous Epileptic Mutations in the Mouse

18. Genetic Models of Absence Epilepsy in the Rat

19. Models with Spontaneous Seizures and Developmental Disruption of Genetic Etiology

20. Mammalian Models of Genetic Epilepsy Characterized by Sensory-Evoked Seizures and Generalized Seizure Susceptibility

21. Inherited Epilepsy in Mongolian Gerbils

D. Acquired Focal Models

22. The Cortical Freeze Lesion Model

23. MAM and Other “Lesion” Models of Developmental Epilepsy

24. In Utero Irradiation as a Model of Cortical Dysplasia

25. Modeling Hypoxia-Induced Seizures and Hypoxic Encephalopathy in the Neonatal Period

26. Complex Febrile Seizures—An Experimental Model in Immature Rodents

27. Repetitive Seizures in the Immature Brain

28. The Kindling Phenomenon

29. Kindling Kittens and Cats

30. Electrical Kindling in Developing Rats

31. Chemical Kindling

32. Kindling, Spontaneous Seizures, and the Consequences of Epilepsy: More than a Model

33. Tetanus Toxin Model of Focal Epilepsy

34. Kainate-Induced Status Epilepticus: a Chronic Model of Acquired Epilepsy

35. The Pilocarpine Model of Seizures

36. Status Epilepticus: Electrical Stimulation Models

37. Posttraumatic Epilepsy Induced by Lateral Fluid-Percussion Brain Injury in Rats

38. Chronic Partial Cortical Isolation

39. Head Trauma: Hemorrhage-Iron Deposition

40. Stroke

41. Models Available for Infection-Induced Seizures

42. Brain Tumour and Epilepsy: A New Neurophysiologic and Neuropathologic Ex Vivo In Vitro Model

43. An Animal Model of Rasmussen’s Encephalitis

E. Models Used for Pharmacological Assessment

44. Therapeutic Assays for the Identification and Characterization of Antiepileptic and Antiepileptogenic Drugs

45. Animal Models of Drug-Refractory Epilepsy

F. Technical Approaches for Model Characterization

46. Monitoring for Seizures in Rodents

47. Imaging Approaches in Small Animal Models

48. Behavioral Characterization of Seizures in Rats

49. Behavioral and Cognitive Testing Procedures in Animal Models of Epilepsy

50. Morphologic Approaches to the Characterization of Epilepsy Models

G. Important Questions

51. Animal Model Development Based on the Human Epilepsies: Which Causes and Syndromes Should Be Modeled?

52. What Good are Animal Models

Index