Epileptogenesis in the Developing Brain: What Can We Learn from Animal Models?

Summary:  Knowledge of the processes by which epilepsy is generated (epileptogenesis) is incomplete and has been a topic of major research efforts. Animal models can inform us about these processes. We focus on the distinguishing features of epileptogenesis in the developing brain and model prolonged febrile seizures (FS) that are associated with human temporal lobe epilepsy. In the animal model of FS, epileptogenesis occurs in ～35% of rats. Unlike the majority of acquired epileptogeneses in adults, this process early in life (in the febrile seizures model as well as in several others) does not require "damage" (cell death). Rather, epileptogenesis early in life involves molecular mechanisms including seizure-evoked, long-lasting alterations of the expression of receptors and ion channels. Whereas transient changes in gene expression programs are common after early-life seizures, enduring effects, such as found after experimental FS, are associated with epileptogenesis. The ability of FS to generate long-lasting molecular changes and epilepsy suggests that mechanisms, including cytokine activation that are intrinsic to FS generation, may play a role also in the epileptogenic consequences of these seizures.