Abstracts

RATIONALE: Despite decades of clinical experience with the ketogenic diet (KD), corroborative experimental data in young animals are limited. The present study was designed to investigate the effects of a KD on pentylenetetrazol (PTZ)-induced seizure severity in immature rats. METHODS: Thirty-eight male Sprague-Dawley rats (22 days postnatal) were divided into two equal groups. The KD group was fasted for a day and then fed a KD (Harlan Teklad TD 96355) consisting of a [fat]:[protein + carbohydrate] ratio of 4.3:1 for 26 days, while the control group was fed a standard rodent chow. Blood was collected to determine the concentration of ?-hydroxybutyrate (?-OHB) on treatment days 0, 20, and 24. Seizures were induced by intraperitoneal injection of PTZ (60 mg/kg) between treatment days 22 and 27. Seizure severity was evaluated by using a scoring system of seizure behaviors: 0, no seizure; 0.5, abnormal behavior; 1, myoclonic jerk; 2, myoclonic jerk with jumping; 3, forelimb clonus with preserving righting reflex; 4, generalized clonic seizure with brief loss of righting reflex; 5, generalized tonic clonic seizure; 6, expire. A greater score represents a more severe seizure. RESULTS: Blood levels of ?-OHB were low (<0.3 mM) and showed no significant differences in both groups on day 0. Animals fed the KD developed an increased level of ketosis that was significantly above the levels found in the control group on days 20 and 24 (p<0.001). The KD group (2.37 ? 0.27) exhibited significantly (p<0.05) lower seizure score than the control group (3.37 ? 0.35). CONCLUSIONS: The KD was previously reported to increase PTZ-induced seizure thresholds in rats. In this study, immature rats fed the KD exhibited significantly decreased PTZ-induced seizure scores relative to controls. This suggests that the KD can not only increase the resistance to seizure but also decrease the severity of seizure induced by PTZ. Supported by Ministry of Health and Welfare (HMP-99-N-02-0003), Korea.