Abstract | PURPOSE: Several findings suggest that energy metabolism and the glutamate- glutamine cycle may be impaired in epilepsy. Positron emission tomography often shows interictal hypometabolism of the epileptogenic hippocampus. In vivo microdialysis studies show that seizure-associated glutamate release is doubled, and clearance is slowed. We hypothesized that the glutamate- glutamine cycle between neurons and glia may be decreased in the epileptic human hippocampus. METHODS: A 20% solution of 2-13C-glucose was infused before resection of the epileptogenic hippocampus. Blood glucose isotopic fractions were measured every 30 min. Blood and brain specimens were frozen quickly; perchloric acid extracts of the small metabolites were prepared and analyzed by proton and carbon magnetic resonance spectroscopy (MRS) at 11.75 Tesla. RESULTS: Standard histology showed 12 with hippocampal sclerosis and five with minimal neuron loss. The relative rates of glutamate- glutamine cycling with respect to glutamate synthesis were decreased in biopsies affected by hippocampal sclerosis (mean, 0.08; 95% confidence interval, 0.04-0.12) compared with those with minimal neuron loss (0.52; 95% CI, 0.30-0.75). Mean cellular glutamate concentrations were higher in minimal neuron loss (8.9 mM; 95% CI, 7.4-10.4) than hippocampal sclerosis (7.3 mM; 95% CI, 5.9-8.7). Cellular glutamine concentrations (mean, 2.8 mM; 95% CI, 2.4-3.2; n = 17) were the same in all groups. CONCLUSIONS: The epileptogenic, gliotic human hippocampus appears to be characterized metabolically by slow rates of glutamate- glutamine cycling, decreased glutamine content, and a relative increase in glutamate content. We hypothesize that the low rate of glutamate- glutamine cycling that results from a failure of glial glutamate detoxification could account for slow glutamate clearance from synapses and continuing low-grade excitotoxicity.
|
Authors | Ognen A C Petroff, Laura D Errante, Douglas L Rothman, Jung H Kim, Dennis D Spencer |
Journal | Epilepsia
(Epilepsia)
Vol. 43
Issue 7
Pg. 703-10
(Jul 2002)
ISSN: 0013-9580 [Print] United States |
PMID | 12102672
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Carbon Isotopes
- Glutamine
- Glutamic Acid
|
Topics |
- Adolescent
- Adult
- Carbon Isotopes
- Citric Acid Cycle
(physiology)
- Energy Metabolism
(physiology)
- Epilepsy
(metabolism)
- Female
- Glutamic Acid
(metabolism)
- Glutamine
(metabolism)
- Hippocampus
(cytology, metabolism, physiology)
- Humans
- Magnetic Resonance Spectroscopy
(methods, statistics & numerical data)
- Male
- Middle Aged
- Neurons
(metabolism)
|