ABSTRACT
Epilepsy is a common, chronic neurological disorder. It is characterized by recurring seizures which are the result of abnormal electrical activity in the brain. Th e molecular pathways underlying cell death are of interest in epilepsy because prolonged seizure episodes (status epilepticus) cause signifi cant neuronal death, particularly within vulnerable brain regions such as the hippocampus. Temporal lobe epilepsy is commonly associated with neuronal loss within the hippocampus and repeated seizures over time in patients with poorly controlled epilepsy may cause additional damage. Biochemical markers of apoptosis have been identifi ed in brain tissue removed from patients who underwent surgery for pharmacoresistant epilepsy. Findings include increased expression of caspases and the presence of their cleaved forms, and altered expression of pro-apoptotic Bcl-2 family genes. However, there is also evidence of anti-apoptotic signaling changes in the same tissue and apoptotic cells are rare in such material. Animal studies have determined that brief and prolonged seizures can cause neuronal apoptosis within the hippocampus. Th is can be associated with caspase and pro-apoptotic Bcl-2 family protein activation and DNA fragmentation. Pharmacological inhibitors of these pathways can reduce DNA fragmentation in these models and spare
neurons from cell death. Th us, apoptosis and its associated signaling pathways are potentially important for pathogenesis of epilepsy and represent novel therapeutic targets for treatment.
