Relationship between Neuronal Loss and Interictal Glucose Metabolism during the Chronic Phase of the Lithium-Pilocarpine Model of Epilepsy in the Immature and Adult Rat

Metabolism is Normal in Astrocytes in Chronically Epileptic Rats: A 13C NMR Study of Neuronal—Glial Interactions in a Model of Temporal Lobe Epilepsy

“…However, this was only statistically significant for unlabeled glucose, not for [1-13 C]glucose, likely because the percentage of enrichment in glucose was only 18%, thus the differences might have been too small to be detectable. This decreased consumption is in agreement with animal and human data showing interictal hypometabolism within the hippocampus, which could extend to extratemporal cortical and subcortical regions (Arnold et al, 1996;Dube et al, 2001;Vielhaber et al, 2003b;Chassoux et al, 2004). Moreover, in these areas neuronal loss does not necessarily correlate with interictal hypometabolism (Ryvlin et al, 1991;O'Brien et al, 1997;Foldvary et al, 1999;Dube et al, 2001).…”

“…Thus, it is not surprising that metabolites in the cerebral cortex were also affected in epileptic Li-pilo rats. Although only moderate cell loss occurs in this area (Turski et al, 1989;Motte et al, 1998;Dube et al, 2001), the decrease in the concentration of neuron-related metabolites such as NAA and aspartate was quite marked, whereas the glutamate level was unchanged. While a decrease in NAA concentration may reflect cell loss in the hippocampal formation, it most likely also reflects neuronal metabolic dysfunction in cortex (Vielhaber et al, 2003a).…”

“…These two validated models of TLE are similar to the human disease in development of seizures, in its pathology and in its pharmalogical response. Pilocarpine or lithium-pilocarpine (Li-pilo)-induced SE, which represents the acute phase of the disease, is characterized by a muscarinic response followed rapidly by a glutamatergic generalization, leading to a large increase in calcium concentration, mitochondrial failure, and extensive necrotic neuronal death, mostly in the hippocampus (CA1, CA3, and hilus of the dentate gyrus), amygdala, thalamus, piriform, and entorhinal cortices (Turski et al, 1989;Motte et al, 1998;Dube et al, 2001). The subsequent latent phase is characterized by repair processes, such as astroglial response, neurogenesis, sprouting, and circuit reorganization, leading to the formation of a hyperexcitable circuit in lesioned limbic regions underlying the expression of spontaneous recurrent seizures (SRS) (Turski et al, 1989).…”

Brain Mitochondrial Metabolic Dysfunction and Glutamate Level Reduction in the Pilocarpine Model of Temporal Lobe Epilepsy in Mice

“…Natural abundance of glucose cannot be reliably calculated as the level of brain glucose before administration of [1,[2][3][4][5][6][7][8][9][10][11][12][13] C]glucose to the animals is unknown. Calculating natural abundance based on measured total glucose amount (1.1% Â 1.1% Â (amount of 12 C glucose þ 13 C glucose)) will overestimate natural abundance, whereas calculating natural abundance based on 12 C glucose concentration (1.1% Â 1.1% Â amount of 12 C glucose) will underestimate 13 C natural abundance.…”

“…14, 15 We utilized 1 H nuclear magnetic resonance (NMR) spectroscopy and highpressure liquid chromatography (HPLC) to obtain detailed maps of the metabolite content in cerebral cortex and hippocampal formation (HF) in pilocarpine-SE mice. To be able to determine glucose metabolism, we injected animals with [1,[2][3][4][5][6][7][8][9][10][11][12][13] C]glucose 15 minutes before microwave fixation of the head, and evaluated brain extracts using 13 C NMR spectroscopy and gas chromatography-mass spectrometry (GC-MS).…”