cDNA profiling of epileptogenesis in the rat brain

Symptomatic temporal lobe epilepsy typically develops in three phases: brain insult --> latency period (epileptogenesis) --> recurrent seizures (epilepsy). We hypothesized that remodeling of neuronal circuits underlying epilepsy is associated with altered gene expression during epileptogenesis. Epileptogenesis was induced by electrically triggered status epilepticus (SE) in rats. Animals were continuously monitored with video-EEG, and the hippocampus and temporal lobe were collected either during epileptogenesis (1, 4 and 14 days) or after the first spontaneous seizures (14 days) for cDNA array analysis. Altogether, 282 genes had altered expression, from which 87 were in the hippocampus and 208 in the temporal lobe (overlap in 13). Assessment of hippocampal gene expression during epileptogenesis indicated that 37 genes were altered in the 1-day group, 12 in the 4-day group and 14 in the 14-day epileptogenesis group. There were 42 genes with altered expression in the 14-day epilepsy group. In the temporal lobe, the number of genes with altered expression was 29 in the 1-day group, 155 in the 4-day group, 32 in the 14-day epileptogenesis group and 62 in the 14-day epilepsy group. Products of the altered genes are involved in neuronal plasticity, gliosis, organization of the cytoskeleton or extracellular matrix, cell adhesion, signal transduction, regulation of cell cycle, and metabolism. As most of these genes have not previously been implicated in epileptogenesis or epilepsy, these data open new avenues for understanding the molecular basis of epileptogenesis and provide new targets for rational development of anti-epileptogenic treatments for patients with an elevated risk of epileptogenesis after brain injury.