Selective hippocampal cell damage and mossy fiber sprouting induced by chronic intracerebral injections of 2-deoxy-D-glucose.

A reduction in glucose consumption has been shown in both patients with acquired epilepsy and in animal epilepsy models. However, the question remains whether the disturbance of glucose metabolism is the driving force of epileptogenesis. We have recently reported that a chronic partial inhibition of brain glycolysis by the non-metabolizable glucose analogue 2-deoxy-D-glucose (2-DG) triggers epileptogenesis in initially healthy rats. In this study, we further investigated whether chronic 2-DG treatment caused a cellular loss in the dorsal hippocampus and mossy fiber sprouting in the dentate gyrus. We found that prolonged (four weeks) treatment with 2-DG induced a neuronal loss in the CA1 field and the dentate hilus. We also found mossy fibers reorganization in the 2-DG group. In addition, we showed that pentylenetetrazole-induced convulsions were considerably strengthened and prolonged in 2-DG-treated rats. Our results demonstrate that the chronically impaired brain glucose metabolism likely leads to a structural remodeling resembling epileptogenesis and has a proconvulsive effect.