Abstracts

Previous reports have suggested that the ketogenic diet (KD) may exert neuroprotective actions. We asked whether the KD reduces neuronal cell death in the CA3/hilar region of the hippocampus after kainic acid-induced status epilepticus, independent of effects on seizure severity. C3HeB/FeJ mice were fed either the Bio-Serv F3666 diet (6:1 ratio of [fats:carbohydrate + protein]; N=14) or normal rodent chow (N=7) for 10-14 days beginning at P21-23. Blood D-[beta]-hydroxybutyrate (BHB) levels were measured using a commercially available reflectance meter. After dietary treatment, each mouse was injected with 20 mg/kg SC kainic acid (KA), and behavioral seizure scores (using a modified Racine scale) were given each minute for 2 hours. Three days after KA injection, mice were sacrificed for histochemistry with Fuoro-Jade B (FJ) and cell counts were conducted of FJ-positive neurons in the CA3/hilar region of the hippocampus. BHB levels 1 day prior to sacrifice were significantly higher for KD-treated vs. control diet-fed mice, respectively (P[lt]0.05). Cumulative seizure scores were 326 [plusmn] 9 and 336 [plusmn] 4 (P = NS) in KD- and SD-groups, respectively. There were significantly less FJ-positive CA3/hilar neurons in KD-fed animals versus controls (left hippocampus: 81 [plusmn] 11 vs. 265 [plusmn] 84, P[lt]0.05). A ketogenic diet is neuroprotective against kainic acid-induced status epilepticus in juvenile mouse hippocampus. This protective effect does not appear to be a consequence of the KD reducing the severity of status epilepticus. (Supported by NIH K02 NS 044846 (JMR).)