The Effects Of Ketogenic Diet On The PTZ-induced Seizure Threshold And The Pathological Changes Of Hippocampus In Immature Rats

IntroductionThe ketogenic diet(KD) is a kind of diet which contains high fat and low protein plus carbohydrate. The clinical studies on the treatment of intractable epilepsy, especially the intractable epilepsy in children by KD were reported 70 years ago. It was considered as a safty and effective method. The animal study on the mechanism of KDs action are becoming the popular topic of epilepsy treatment in the foreign countries.In our study, in order to explore the anticonvulsant effect of KD on the experimental rats and observe the effect of KD on the seizure intensity, we designd to determinate the PTZ - induced seizure threshold of immatrure rats fed with KD and to observe their morphological changes in the hippocampus consulting the foreign relative document data.Materials and MethodsWe divided 40 healthy 25-30days old Wistar rats into two groups randomly. They are experimental group(KD group) and control group (normal diet group). Every group has 20 naive rats. They were fed with ketogenic diet and normal diet respectively after 12 hours fast. The KD is the mixture of lard and the rodent chow by the ratio of 4:1 (fat:protein plus carbohydrate by weigh). Ten days later,seizures were chemically induced by tail-vein infusion of PTZ( concentration: 10mg/ml;infusion rate: 1.0ml/min). The threshold dose of PTZ( mg/ kg) was derived from the time required to produce the first bilateral myoclonic twitch of the forelimbs and the seizure behaviore were noted for scoring. Then the subepileptogenic dose of PTZ was administered intraperitoneally to the rats every other morning until to the kindling state. All rats were anesthetized and infusion fixing. The hippocampus slides were prepared for HE staining. The morphological changes in hippocampus formation were studied and the normal neuron cells in hippocampus CA3 area were counted.Results1. Animals Animals freely consumed the ketogenic diet did not show any signs of ill health. The increased animal body weight of control group was a little more than that of the experimental group.2. Effects of the ketogenic diet on seizure threshold and the seizure severity Rats fed with the ketogenic diet showed an increasd resistance to seizure and a higher seizure threshold than the controlgroup animals(p<0.01). But there was no obvious difference of seizure severity between them(P>0.05)3. Morphological study The neuron cells in hippocampus CA1 CA3area and dental gyrus of all animals showed degenerated and necrosis, and the severity of control group was more obvious than that of the KD group. The counts of normal neuron cells in hippocampus CA3 area of KD group are higher than that of the control group (P<0. 01).DiscussionThe ketogenic diet is designed to induce continuous systemic ke-tosis. It is based on very low carbohydrate and very high fat intake. The classic KD,which was used to control seizures, has a ratio of fat to protein plus carbohydrate of 4:1. The fat is derived from animal sources. Clinical and animal studies had showed that the experimental subjects could produce a steady ketonemia level and had the anticon-vulsant effect after 5-7days on KD. Ketonemia has been showed to result from consumption of high - fat diets. It was the basis of the seizure protection. We should emphasized that many clinical studies had suggested that we can gain more obvious and safty effect in the KD treatment of children intractable epilepsy. Because children had show to develop higher level of ketonemia. So in our study we choosed 30 days old rats and kept them on KD for 10 days.We had found in our study that the seizure threshold of KD group are higher than that of control group. The difference are stastically significant. But the seizure severity showed no obvious difference. This indicated that KD can elevate the PTZ - induced seizure threshold, butdonot change the seizure severity. Thease findings were also confirmed by Kristophe. J et al. However, some researchers had suggested in their studies that KD had a proconvu...