Mapping of the progressive metabolic changes occurring during the development of hippocampal sclerosis in a model of mesial temporal lobe epilepsy

We have recently characterized the histopathological changes in an experimental model of mesial temporal lobe epilepsy (MTLE) induced by the intrahippocampal injection of low dose of kainate in mice. Although cerebral metabolism and blood flow are extensively studied and used in human MTLE to locate the regions involved in seizures before surgery, this exploration is only performed once the disease has fully developed. Therefore, in the present study, we followed the temporal evolution of intrahippocampal kainate-induced metabolic changes in mice from kainate injection to 120 days later by the quantitative autoradiographic [C-14]2-deoxyglucose (2DG) technique. At day 0 (late phase of status epilepticus (SE)) and 15 days after kainate, i.e., during the period of ongoing neuropathological changes, glucose utilization was decreased bilaterally in all parts of the cerebral cortex, and ipsilaterally in the thalamus. In the hippocampus, CA1 metabolic activity was depressed at day 0 and increased at day 15 while CA3 glucose utilization was increased at both day 0 and 15. By day 30, there were almost no pyramidal cells left in the two hippocampal regions. At day 120, ipsilateral decreases persisted in the entorhinal cortex, anterior and ventromedian thalamus, and metabolic increases were recorded bilaterally in the central amygdala, anterior hypothalamus and mamillary body. At all times after kainate, a normo-, hypo- or hypermetabolic level was recorded in the dentate gyrus. The present study shows that the process of hippocampal sclerosis involves bilateral cortical reactivity and the participation of some limbic forebrain and motor structures. When hippocampal sclerosis has fully developed, hypometabolism is limited to regions directly connected to the damaged hippocampus and most likely involved in the new hyperexcitable circuit of limbic seizures. (C) 2000 Elsevier Science B.V. All rights reserved.