Abstracts

Status epilepticus(SE) induced by kainic acid (KA) in adult rats produces a marked neuronal loss and chronic epilepsy and acts as a model of temporal lobe epilepsy. In contrast, in young rats prior to postnatal day 18 (P18), KA injection causes neither cell death nor chronic spontaneous seizures. To elucidate the mechanisms behind this differential response, we utilized microarray and quantitativen(q) RT-PCR to assess transcriptional alterations after KA-induced SE in P15 and P30 rat hippocampi. LE male rats were injected either with PBS (control) or KA at P15 or P30 and hippocampi were isolated at 1, 6, 24, 72, or 240 h post-seizure. Total RNA was isolated from 12 hippocampi and pooled for triplicate Affymetrix genechips. Microarray results were validated by qRT-PCR with independent RNA samples. Genes in several functional groups were highly regulated by KA-induced SE in immature and mature rat hippocampi. Inflammation-related genes comprised the most abundant functional group significantly regulated after KA. Neuropeptides were also significantly regulated by seizures in both age groups. Cortistatin uniquely showed high expression in P15 and was further increased after KA only in P15. A rapid and transient induction of genes coding for classical inflammatory mediators and neuropeptides on P15. In contrast, KA at P30 induced inflammatory transcripts and neuropeptides to a significantly greater extent. Several structurally-related genes (Map2, Map1b, Mapre1 and [alpha]-tubulin) were differentially regulated after KA in P15 vs P30. Genes in the stress response functional group showed similar patterns of expression increase with peaks in levels of heat-shock proteins, Hsp27 and Hspa1a, and heme oxygenase 1 at 6-24 h post-SE. While expression levels of Hspa1a and Hmox1 returned to near baseline levels in both age groups by 72 h, Hsp27 expression remained elevated at 240 h in P30 samples. Expressions of cell adhesion genes(Galectin-3, secreted phosphoprotein 1, Fibronectin) were similarly altered by SE in both age groups. These results show a differential response in gene expression after KA-induced seizure in young versus adult rats. The overall gene expression pattern in P15 hippocampi showed a transient response with most genes returning to baseline by 72 h. In contrast, transcriptional alterations after KA in P30 were sustained. This differential expression response following KA-induced SE may reflect genomic responses that will offer insight into the unique mechanisms of neuroprotection in immature brain that could ultimately be adapted as treatments for adults to prevent seizure-induced neuronal loss and subsequent cognitive dysfunction. (Supported by K088NS02068 and Davee Foundation.)