Abstracts

RATIONALE: Seizure incidence varies significantly with age, with seizure susceptibility particularly high during the first few years of life. Of significant concern is what effects do brief, repetitive seizures have on the developing brain. We approached this issue by examining the change in seizure threshold and related metabolic markers as a function of multiple seizure episodes. METHODS: Immature (P15) and adult (P60) Sprague-Dawley rats were given two flurothyl seizures a day for 5 days (9 or 10 seizures). Threshold was measured as latency to first myoclonic jerk (MJ) and to generalized seizure (G). On day five of testing, just prior to the 9th or 10th seizure, [14C]-2 deoxyglucose (2DG) was administered through the lateral tail vein. All animals were sacrificed 45 min after injection of 2DG. c-Fos mRNA measures were obtained from the same brain sections used for 2DG analysis. RESULTS: The animals were divided into 4 groups: sham (no) seizures; single seizures, and 9 or 10 seizures. Immature and adult rats showed different seizure profiles across the five days. Thresholds for the second seizure in immature rats on each day were significantly lower (MJ & G) than for the first seizure. In adult rats, the first three days of testing, seizure thresholds (MJ & G) were significantly higher for the second seizure. In immature animals, 2DG labeling was generally lower in the 9/10 seizure groups compared to sham/single seizure groups. In contrast, c-fos mRNA expression was highly region dependent, with some areas (e.g., striatum and neocortex) showing lower c-fos levels in multiple seizure animals and some areas (e.g., locus coeruleus and hippocampus) showing higher c-fos expression. CONCLUSIONS: The immature animals displayed no refractoriness after the first seizure of each day (decreased thresholds). While c-fos expression (at least in some regions) higher in young animals with multiple seizures compared to rats with no (single) seizures, 2DG showed a decrease in multiple seizures rats. These latter results support the view that immature rats use metabolic pathways (and/or glucose transporters) different from those used by adult animals. [Supported by VAMC and NIH NS 18895]