ABSTRACT
Epilepsy is the most prevalent serious neurological disorder, afflicting almost 1% of the population worldwide.1,2 It is a heterogeneous disorder, comprising numerous syndromes with a wide range of etiologies,3 that is defined by the manifestation of chronic spontaneous recurrent seizures (CSRSs). An epileptic seizure, in turn, is defined by the International League Against Epilepsy (ILAE) as “transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.”4,5
Post-traumatic epilepsy (PTE) arises after mechanical damage to the brain and is diagnosed when spontaneous seizures are observed at least a week after brain injury. PTE is the most prevalent acquired epilepsy in young adults and accounts for 5% of epilepsies overall.6,7 There are currently no cures for PTE and no means to prevent the disorder in those at risk.8 Available treatments of PTE are symptomatic,
Introduction ............................................................................................................ 219 What to Model...................................................................................................220 Animal Models of Post-Traumatic Epilepsy ..................................................... 221
Model Optimization for Therapy Development ..................................................... 222 Assessing Epilepsy Treatments with Fluid Percussion Injury-Induced PTE .........226 Technical and Methodological Issues in PTE Therapy Development ................... 227
Definition of Epilepsy and of Seizures.............................................................. 227 Detection of Epileptic Seizures .........................................................................228 Avoiding Experimental Bias .............................................................................230 Using the Right Control Groups ....................................................................... 231
Sham Injury and Electrode Damage ............................................................. 231 Impact of Rat Strain, Age, and Gender on Idiopathic Seizures .................... 231
Conclusions ............................................................................................................ 232 Acknowledgments .................................................................................................. 233 References .............................................................................................................. 233
and at least 40% of patients have seizures that cannot be controlled with any of the available drugs.9,10 This dire situation requires rethinking the development and use of animal models for the development of therapies for PTE.11,12 In this chapter we will introduce the problem and discuss several topics crucial for modeling PTE for therapy development.
