Drug-mediated neuroprotection and antiepileptogenesis: animal data

Seizures have a partial onset in approximately two-thirds of epilepsy patients. In most of these cases epilepsy is a consequence of a brain-damaging insult such as head trauma, stroke, brain infection, brain surgery, or status epilepticus. The epileptic process consists of three phases: initial insult U27AA; latency period (epileptogenesis) U27AA; recurrent seizures (symptomatic epilepsy). The treatment of epilepsy focuses exclusively on preventing or suppressing seizures, which are the end products of the epileptic process. The challenge is whether epileptogenesis can be prevented by therapeutic intervention. If not, can the disease process be modified in such a way that epilepsy will be easier to treat? Achieving these goals is becoming more realistic now that there is a better understanding of the neurobiology of the epileptic process and the factors that predict the risk for progression in individual patients. These data provide new opportunities for the design of neuroprotective and antiepileptogenic treatments for patients who, if untreated, could develop drug-refractory epilepsy associated with cognitive decline. Here we review the available data on neuroprotective, antiepileptogenic, and disease-modifying effects of antiepileptic drugs and other treatments at different phases of the epileptic process. Analysis of these data suggests that by using compounds currently available, beneficial effects on the outcome can be achieved by modification of the epileptogenic insult at the acute phase and by modification of circuitry reorganization that is induced/maintained by brief seizures after the diagnosis of epilepsy. Discontinuation or modification of epileptogenesis in patients who experienced an epileptogenic insult months or years before is more complicated. However, molecular screening of candidate epileptogenesis-related genes has revealed novel mechanisms underlying network reorganization and will undoubtedly provide exciting avenues for the development of true antiepileptogenic and disease-modifying agents.