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We suggest that a dysregulation of energy metabolism in the brain of genetic absence epilepsy rats from Strasbourg (GAERS) could create a specific cerebral environment that would favor the expression of spike-and-wave discharges (SWD) in the thalamocortical loop, largely dependent on glutamatergic and gamma-aminobutyric acid (GABA)-ergic neurotransmissions. We tested several aspects of metabolic activity in the brain of GAERS compared to a genetic strain of nonepileptic (NE) rats. Glucose metabolism was higher in all brain regions of GAERS compared to those of NE rats along the whole glycolytic and aerobic pathways, as assessed by regional histochemical measurement of lactate dehydrogenase and cytochrome oxidase activities. Branched-chain amino acids (BCAA) and alpha-ketoisocaproate (alpha-KIC), the ketoacid of leucine, when injected intraperitoneally, increased the number of SWD in GAERS but had only a slight effect on their duration. These data speak in favor of a BCAA- or alpha-KIC-induced change in neuronal excitability. Leucine and alpha-KIC decreased the concentration of glutamate in thalamus and cortex without affecting GABA concentrations. Thus, BCAA and alpha-KIC, by decreasing glutamatergic neurotransmission, could favor GABAergic neurotransmission, which is known to increase the occurrence of seizures in GAERS. Finally, the transport of [1-(14)C]alpha-KIC in freshly isolated cortical neurons was lower in GAERS than in NE rats, and this difference was shown to be of metabolic origin. The addition of gabapentin, a specific inhibitor of BCAA transaminase (BCAT), reduced the transport of [1-(14)C]alpha-KIC in GAERS and NE rats to a level that became identical in both strains. This strain-dependent change was not related to a difference in the activity of BCAT, which was identical in GAERS and NE rats. The exact origin of this apparent metabolic dysregulation of energy metabolism in GAERS that could underlie the origin of seizures in that strain remains to be explored further., (Copyright 2001 Wiley-Liss, Inc.)

The transport of L-carnitine (4-N-trimethylammonium-3-hydroxybutyric acid) was studied with a primary culture of porcine brain capillary endothelial cells (BCEC) as an in vitro model of the blood-brain barrier. The measurements with suspended cells and cell monolayers allowed to distinguish a polarized transport phenomena. The part of the BCEC cells exposed to the medium (apical membrane) accumulated carnitine by a sodium-independent, saturable (Km=28 microM) system, with k=0.018 min-1. Exposure of the basolateral part revealed a presence of a facilitated diffusion process. Carnitine uptake through the saturable system was inhibited by butyrobetaine. Acylcarnitines and choline have no effect on the carnitine accumulation in suspended cells, a process diminished by phenylalanine, leucine, and L system inhibitor. This points to the possibility that carnitine enters through the basolateral membrane using amino acid transporting systems. A different, novel system is postulated to operate in the apical part of the plasma membrane of BCEC., (Copyright 1997 Academic Press.)