Regulation of Inflammation-Related Genes through Suppression in a Levetiracetam-Treated Pilocarpine-Induced Status Epilepticus Mouse Model.

Levetiracetam (LEV) suppresses the upregulation of proinflammatory molecules that occurs during epileptogenesis after status epilepticus (SE). Based on previous studies, LEV likely helps prevent the onset of epilepsy after insults to the brain, unlike other conventional anti-epileptic drugs. Recently, we discovered that the increase in expression that occurs after lipopolysaccharide (LPS) stimulation is suppressed by LEV and that inhibition suppresses inflammation in BV-2 microglial cells. These data indicate that is an important target of LEV and a key factor in preventing epilepsy onset. In this study, we examined the effects of LEV on expression and neuroinflammation in vivo. During epileptogenesis, the post-SE upregulation of hippocampal levels of and many inflammatory factors were suppressed by LEV. expression showed a characteristic pattern different from that of the expression of , an immediate-early gene belonging to the same Fos family. At 2 days after SE, was predominantly expressed in astrocytes but was rarely detected in microglia, whereas expression was distributed in various brain cell types. The expression of A2 astrocyte markers was similar to that of and was significantly suppressed by LEV. These results suggest that LEV may regulate astrocyte reactivity through regulation of .