Norepinephrine is required for the anticonvulsant effect of the ketogenic diet

Ketogenic diet (KD) is a high fat, low carbohydrate diet used to treat chil dren with epilepsy that are refractory to conventional antiepileptic drugs (AEDs). The anticonvulsant mechanism of the KD is unknown. To determine if the noradrenergic system has a role in mediating the anticonvulsant action of the KD, dopamine beta -hydroxylase knockout (Dbh -/-) mice that lack nor epinephrine (NE) and Dbh +/- littermates that have normal NE content were f ed either a standard rodent chow or the KD. When exposed to the convulsant flurothyl, Dbh +/- mice fed the KD had significantly longer latencies to my oclonic jerk (MJ) and generalized clonic-tonic (CT) seizures than Dbh +/- m ice fed normal chow. In contrast, Dbh mice fed the KD had seizure latencies to both MJ and CT comparable to Dbh -/- mice fed normal chow. These result s suggest that an intact, functional noradrenergic nervous system is requir ed for the KD to exert an anticonvulsant effect. Published by Elsevier Scie nce B.V.