Effect and mechanism of ketogenic diet on neurobehavioral demages induced by recurrent neonatal seizures

Objective To investigate the intervention effect of ketogenic diet (KD) on neurobehavioral demages after flurothyl-induced recurrent neonatal seizures in rats and on the expression of ApoE. Methods Postnatal day 8 (P8) SD rats (quantity: 48) were randomly divided into two groups: the non-seizure group (NS group, n=24) and the recurrent-seizure group (RS group, n=24). From P9, rats in RS group were subjected to recurrent seizures induced by volatile flurothyl 30 min each day for consecutive 8 days. While rats in NS group were placed into the container for an equal amount of time to their counterpart without exposuring to flurothyl. At P28, each group was divided into two groups again: non-seizure and normal diet group(NS+ ND group, n=12), non-seizure and ketogenic diet group(NS+ KD group, n=12), recurrent-seizure and normal diet group(RS+ ND group, n=12), recurrent-seizure and ketogenic diet group(RS+ KD group, n=12). At P42, neurodevelopmental indicators were monitored. ApoE protein levels in cerebral cortex were determined by western blot at P58. Results Neurodevelopmental indicators were analyzed at P42: in the plane righting experiment, the rats of group NS+ ND (1.0±0.14) about the time of plane righting was significant different comparing with group RS+ ND ((0.75±0.32)s)(P 0.05). In the negative geotaxis reaction experiment, the rats of groups NS+ KD and RS+ ND((3.17±0.58)s, (6.75±0.75)s) about the time of negative geotaxis reaction were significant different comparing with group NS+ ND ((1.58±0.52)s)(P<0.05). Compared with group RS+ ND, the group RS+ KD in the time of negative geotaxis reaction was obviously shortened(P<0.05). In the cliff avoidance test, there were significant differences between group NS+ ND、RS+ KD ((5.75±2.90)s, (9.50±4.36)s)and group RS+ ND((14.00±4.79)s) about the time of cliff avoidance(P<0.05). In western blot, the expression of ApoE in cerebral cortex in the RS+ ND group (1.26±0.30) was obviously increased compared with group NS+ ND (0.78±0.12) (P<0.05), and there had also significant difference between group RS+ KD (0.89±0.10) and group RS+ ND(P<0.05). Conclusion The neuroprotective effects of ketogenic diet on recurrent neonatal seizure-induced neurobehavioral demages may be associated with the reduction of ApoE in cerebral cortex. Key words: Neonatal seizure; Ketogenic diet; Neurobehavior; ApoE