The tetanus toxin model of chronic epilepsy

In experimental models of epilepsy, single and recurrent seizures are often used in an attempt to determine the effects of the seizures themselves on mammalian brain function. These models attempt to emulate as many features as possible of their human disease counterparts without many of the confounding factors such as underlying disease processes and medication effects. Numerous models have been used in the past to address different questions. Nevertheless, the basic questions are often the same: 1. Do seizures cause long-term damage? 2. Do seizures predispose to chronic epilepsy (epileptogenesis), that is long-term spontaneous repetitive seizures? 3. Are these results developmentally regulated? 4. Are the underlying mechanisms of epileptogenesis and brain damage related? In pursuing these questions, the goal is to determine how seizures exert their effects and to minimize any side effects from the methods employed to induce the seizures themselves. This requires a detailed characterization of the methods used to induce seizures. In this chapter, we will review the literature regarding the tetanus toxin model of chronic epilepsy with regard to its mechanisms of action, clinical comparisons, how it is experimentally implemented and the results obtained thus far. These results will be compared to other models of chronic epilepsy in order to make generalizations about the effects of repetitive seizures in adult and early life. At this time, it appears that repetitive seizures cause long-term changes in learning ability and may cause a predisposition to chronic seizures at all ages. In younger animals, both features of learning impairment and epilepsy are not typically associated with cell loss as they are in adult animals. At all ages, some form of synaptic reorganization has been demonstrated to occur.