Models of Seizures and Epilepsy

Dr. Pitkänen is currently a Professor of Neurobiology at the University of Eastern Finland in Kuopio, Finland. She has over a 30 years’ experience in working and developing animal models of acquired epilepsy and phenotyping of epilepsy models, using histologic and molecular analysis, behavioral tests, long-term video-EEG and MRI imaging. She is a leader in epilepsy research and has participated in several NINDS on Epilepsy Models Workshops and worked in several ILAE Committees related to preclinical modelling and use of models to develop better therapies for epilepsy. She has an h-index of 52 and has over 279 publications. Dr. Buckmaster is an Associate Professor of Comparative Medicine and Neurology at Stanford University School of Medicine in Stanford, California. His laboratory uses electrophysiological and anatomical techniques to evaluate neuronal circuitry of temporal lobe structures in normal and epileptic brains. He is a veterinarian with 25 years of experience investigating mechanisms of temporal lobe epilepsy using anatomical and electrophysiological techniques. He has worked with a variety of mammalian species, including primates, carnivores, and rodents. He has an h-index of 29 and has published over 74 articles. Dr. Galanopoulou is an Attending Physician at the Clinical Neuroscience Center and EEG lab at Montefiore, a Professor of Neurology and Neuroscience at Albert Einstein College of Medicine in Bronx, New York. She is also the co-chair of the AES/ILAE Translational Research Task Force of the ILAE, which works towards the optimization of the use of animal models of seizures, epilepsies, and comorbidities in epilepsy research. She is a clinical epileptologist with 15 years’ experience with epilepsy basic research using a variety of animal models and particularly models of early life seizures and epilepsies. She has an h-index of 29 and has published over 84 articles. Dr. Moshé is the is the Charles Frost Chair in Neurosurgery and Neurology and Professor of Neurology, Neuroscience, and Pediatrics at Albert Einstein College of Medicine. He is the Director of Child Neurology and Clinical Neurophysiology Dr. He has been President of the International League Against Epilepsy, American Epilepsy Society and American Clinical Neurophysiology Society (1996-1997). He is the recipient of several honors and awards, including Teacher-Investigator Development Award; Jacob Javits Neuroscience Investigator Award from NIH; Michael Prize for Achievement in Epilepsy Research; The American Epilepsy Society Research Award; Ambassador for Epilepsy Award from the International League Against Epilepsy; the Gloor Award from the American Clinical Neurophysiology Society; J.E. Purkyne Honorary Medal in Biomedical Research by the Czech Academy of Sciences; the 2008 Mentor of the Year Award from Albert Einstein College of Medicine; The 2010 Global and Awareness Award from Citizens United for Research in Epilepsy; the First Saul R. Korey Award in Translational Science and Medicine, Albert Einstein College of Medicine in 2012; elected Foreign Member of the Russian Academy of Sciences and Fellow of the American Epilepsy Society 2016. Since 1979, his research has focused on understanding the mechanisms underlying age-related differences in epilepsy in humans and in animal models.

Introduction 1. What can we model? 2. Comparative biology and species effects on expression of epilepsy 3. Strain effects on expression of seizures and epilepsy 4. Good welfare practice in modeling seizures and epilepsy 5. Ethics in the Use of Animal Models of Seizures and Epilepsy 6. Regulatory aspects of drug development 7. Use of animal models for epilepsy research and therapy development

Technical and methodological issues 8. Monitoring for Seizures in Rodents 9. Behavioral characterization and scoring of seizures in rodents 10. Seizure mimics 11. Characterization of pathology 12. Monitoring cardiorespiratory and other physiological parameters during seizures in small animals 13. Behavioral and cognitive testing procedures in animal models of epilepsy 14. In vivo Imaging in rodents

In vitro and in silico models 15. Hippocampal in silico models of seizures and epilepsy 16. Neocortical/thalamic in silico models of seizures and epilepsy 17. iPS cells, stem cells 18. Hippocampus in vitro 19. Thalamus and cortex in vitro 20. Brain slices from human resected tissues 21. Organotypic Hippocampal Slice cultures as a Model of Post-traumatic Epileptogenesis 22. The in vitro isolated guinea pig brain in the study of ictogenesis

Non-mammalian in vivo models  23. Nematode C. elegans: Genetic Dissection of Pathways Regulating Seizure and Epileptic-like Behaviors  24. Drosophila 25. Xenopus laevis 26. Zebrafish models of epilepsy and epileptic seizures

Naturally occurring seizures and epilepsies in animals 27. Veterinarian’s perspective 28. Naturally occurring epilepsy and status epilepticus in dogs 29. Naturally Occurring Temporal Lobe Epilepsy in Cats 30. Naturally occurring epilepsy and status epilepticus in Sea lions 31. Baboon Model of Genetic Generalized Epilepsy 32. Genetic Models of Reflex Epilepsy and SUDEP in Rats and Mice 33. Genetic models of absence epilepsy in rats and mice

In vivo mammalian models of induced seizures and status epilepticus 34. Electrical stimulation 35. Systemic Chemoconvulsants Producing Acute Seizures in Adult Rodents 36. Focally applied chemoconvulsants 37. Models of Chemically-Induced Acute seizures and Epilepsy: Toxic compounds and drugs of addiction 38. Pharmacologically induced animal models of absence seizures 39. Models of seizures and status epilepticus early in life

In vivo mammalian models of acquired epilepsies 40. Tetanus toxin 41. Post-SE models: Systemic kainic acid 42. Post-SE models: Focal kainic acid 43. The Pilocarpine Model of Acquired Epilepsy 44. Post-Status Epilepticus models: Electrical stimulation 45. Post-SE models: Hyperthermia 46. Epilepsy after TBI 47. Post-infectious epilepsy 48. Post-perinatal hypoxia 49. Perinatal Hypoxic-Ischemic Encephalopathy: A Model of Stroke-Induced Pediatric Epilepsy 50. Post-stroke epilepsy 51. Animal Models of Drug-Refractory Epilepsy

In vivo mammalian models of genetic epilepsies with identified gene 52. Spontaneous and Gene-Directed Epilepsy Mutations in the Mouse 53. Dravet and GEFS+ syndromes 54. Tuberous sclerosis and other toropathies

Modeling conditions that predispose to seizures or epilepsy 55. Kindling (including fast and slow kindlers) 56. Human mutations associated with brain malformations resulting in hyperexcitability in rodents 57. Dysplasias - Cortical freeze lesion 58. Dysplasia – MAM, model of developmental epilepsy 59. Dysplasias - In utero irradiation 60. Undercut cortex 61. Brain tumor–related epilepsy 62. Withdrawal seizures 63. Perimenstrual seizures and neurosteroid withdrawal 64. Metabolic disturbances: Hypo- and hyperglycemic seizures in vivo and in vitro 65. Stress 66. Blood Brain Barrier disruption 67. Experimental models of inflammation in epilepsy research

Other specific epilepsy-related syndromes 68. Infantile spasms 69. Models of epileptic encephalopathies 70. Sudep Animal Models

Animal models of other brain diseases with altered seizure susceptibility 71. Epilepsy in Models of Alzheimer’s disease 72. Animal Models of Acquired Epilepsy and Tauopathies 73. Epilepsy in other neurodegenerative disorders: Huntington’s and Parkinson’s diseases 74. Animal models of other brain diseases with altered seizure susceptibility: Autism and Fragile X Syndrome 75. Epilepsy in Models of Rett syndrome 76. Models of depression

Conclusions 77. What do models model? What needs to be modeled?