Blood-brain barrier, ion homeostatis and epilepsy: possible implications towards the understanding of ketogenic diet mechanisms.

[pyruvate dehydrogenase deficiency]

The finding that epileptic seizures alter blood -brain barrier (BBB ) properties has stimulated interest into the possibility that phenotypic changes in brain endothelium may constitute a pathological initiator leading to seizures . Recent evidence obtained from epileptic patients undergoing cortical resection , demonstrated abnormal expression of glucose transporter molecules (GLUT 1 ), while [18 F ]deoxyglucose PET studies demonstrated regions of decreased glucose uptake and hypometabolism in seizure foci . The properties of other 'nonexcitable CNS cells ' are also altered in epileptic tissue , and glial cells from epileptic brain displayed diminished capacity for ionic homeostasis ; voltage-dependent mechanisms were primarily affected , increasing reliance on energy-dependent mechanisms . Diminished ion homeostasis together with increased metabolic demand of hyperactive neurons may further aggravate the neuropathological consequences of BBB loss of glucose uptake mechanisms . Since ketone bodies can provide an alternative to glucose to support brain energy requirements , it is hypothesized that one of the mechanisms of the ketogenic diet in epilepsy may relate to increased availability of beta -hydroxybutyrate , a ketone body readily transported at the BBB . This hypothesis is supported by the fact that the ketogenic diet is the treatment of choice for the glucose transporter protein syndrome and pyruvate dehydrogenase deficiency , both associated with cerebral energy failure and seizures .