title: Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium-pilocarpine model of epilepsy.
abstract: OBJECTIVE
  The metabolic and biochemical changes that occur during epileptogenesis remain to be determined. (18) F-Fluorodeoxyglucose positron emission tomography (FDG-PET) and proton magnetic resonance spectroscopy ((1) H MRS) are noninvasive techniques that provide indirect information on ongoing pathologic changes. We, therefore, utilized these methods to assess changes in glucose metabolism and metabolites in the rat lithium-pilocarpine model of epilepsy as markers of epileptogenesis from baseline to chronic spontaneous recurrent seizures (SRS).
  
  
  METHODS
  PET and MRS were performed at baseline, and during the acute, subacute, silent, and chronic periods after lithium-pilocarpine induced status epilepticus (SE). Sequential changes in glucose metabolism on (18) F-FDG PET using SPM2 and the ratios of percent injected dose per gram (%ID)/g of regions of interest (ROIs) in the bilateral amygdala, hippocampus, basal ganglia with the thalamus, cortex, and hypothalamus normalized to the pons were determined. Voxels of interest (VOIs) on (1) H MRS were obtained at the right hippocampus and the basal ganglia. NAA/Cr levels and Cho/Cr at various time points were compared to baseline values.
  
  
  RESULTS
  Of 81 male Sprague-Dawley rats, 30 progressed to SRS. (18) F-FDG PET showed widespread global hypometabolism during the acute period, returning to baseline level during the subacute period. Glucose metabolism, however, declined in part of the hippocampus during the silent period, with the hypometabolic area progressively expanding to the entire limbic area during the chronic period. (1) H MRS showed that the NAA/Cr levels in the hippocampus and basal ganglia were reduced during the acute period and were not restored subsequently from the subacute to the chronic period without any significant change in the Cho/Cr ratio throughout the entire experiment.
  
  
  CONCLUSIONS
  Serial metabolic and biochemical changes in the lithium-pilocarpine model of epilepsy indirectly represent the process of human epileptogenesis. Following initial irreversible neural damage by SE, global glucose metabolism transiently recovered during the subacute period without neuronal recovery. Progressive glucose hypometabolism in the limbic area during the silent and chronic periods may reflect the important role of the hippocampus in the formation of ongoing epileptic network during epileptogenesis.
authors.affiliation: Department of Neurology, Ulsan University Hospital, Ulsan, Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Lee
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Park
authors.forename: Ki Chun
authors.initials: KC
authors.lastname: Im
authors.forename: Sang Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Chul-Woong
authors.initials: CW
authors.lastname: Woo
authors.forename: Jin Hwa
authors.initials: JH
authors.lastname: Chung
authors.forename: Ki Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kim
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Shon
authors.forename: Yeong In
authors.initials: YI
authors.lastname: Kim
authors.forename: Joong Koo
authors.initials: JK
authors.lastname: Kang
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001931:Brain Mapping; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D018021:Lithium Chloride / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010862:Pilocarpine / Q000633:toxicity*; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014316:Tritium
chemical_list: D010862:Pilocarpine; D019788:Fluorodeoxyglucose F18; D014316:Tritium; D001224:Aspartic Acid; C000179:N-acetylaspartate; D018021:Lithium Chloride; D005947:Glucose; D003401:Creatine; D002794:Choline