A further intriguing model that may address a common mechanism in many epilepsies is disruption of the blood-brain barrier. It has been recently shown that focal disruption of the blood-brain barrier results in development of a hyperexcitablc focus.15,16 Since blood-brain barrier disruption is a common feature of status epilepticus, ischemia, trauma, and CNS tumors, it may be that this is a common mechanism for hyperex citability in these models. The proliferation of these and other models has led to an intense discussion in the Inhibitors,research,lifescience,medical field regarding the validity of such models for the human condition. A worthwhile aspect of this discussion

is that it has led to an awareness that animal Inhibitors,research,lifescience,medical models only replicate specific aspects of any human selleck condition, and it is paramount to be aware of the areas where a specific model is informative versus the ones where it is not. What are the key questions that have been addressed in studies of epileptogenesis? Firstly, experiments primarily in post-status models of epileptogenesis have addressed

the role of changes in voltage-and transmitter-operated ion channels in epileptogenesis. Generally, activity-dependent changes in neuronal function can be subdivided into changes in synaptic communication between neurons (termed synaptic plasticity), and changes Inhibitors,research,lifescience,medical in intrinsic membrane properties of neurons (termed intrinsic plasticity) that govern how synaptic input is integrated. Work on synaptic plasticity has Inhibitors,research,lifescience,medical focused on changes in the expression and function of neurotransmitter receptors at synapses, as well as changed properties of presynaptic neurotransmitter release. Research on intrinsic plasticity has addressed changes in voltage-gated ion channels in the somatic, dendritic, and axonal membrane of neurons.17 There have been multiple such changes described convincingly in the Inhibitors,research,lifescience,medical literature. A crucial question is how to evaluate the role of individual molecular changes seen in animal models in the development

of epilepsy. There are several strategies that could be used to this end. Perhaps the most straightforward Carnitine dehydrogenase of these is to specifically interfere genetically or pharmacologically with ion channel regulation. Due to the novel genetic tools available in recent years, this is becoming more and more feasible. To transfer these types of studies to the human is more difficult. As stated above, human tissue obtained from epilepsy patients reflects the end stage of chronic epilepsy in most cases. It is therefore doubtful that human tissue can serve as a useful control for animal models at an early stage of epileptogenesis. One avenue which may provide a useful link between animal models and human epilepsy, however, is the use of genetic techniques to address whether polymorphisms in ion channel genes, associated proteins, or relevant transcription factors are associated with an increased propensity to develop epilepsy.