EPILEPTOGENESIS | Gene Expression in Immature and Mature Hippocampus After Status Epilepticus

Abstract

Effective therapy is currently limited for childhood epilepsy because little is known about the cellular and molecular changes caused by seizures in the developing brain. This situation is different for the adult epilepsies, where works on numerous animal models have led to important insights about underlying bases of the seizure condition. For example, kainic acid (KA)-induced seizures have been studied as an animal model for status epilepticus (SE) and temporal lobe epilepsy for more than three decades. KA injections in mature rats result in the development of spontaneous seizures and a distinctive pattern of neurodegeneration resembling hippocampal sclerosis in human patients. In younger rats, however, KA-induced SE does not cause spontaneous seizures or cell death. Indeed, the impact of seizures has been less well-studied in younger rats than in adult rats. Recently available microarray technology enables us to look at the complex molecular changes in a genome-wide survey. With this tool, we have investigated age-specific, time-dependent changes in gene expression after KA-induced seizures, and compared the brain transcriptomes in mature and immature rats. Understanding how differently the immature and mature nervous systems respond to seizures could ultimately lead to new interventions to prevent seizure-induced neuronal loss and/or subsequent cognitive dysfunction.