title: N-acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus.
abstract: BACKGROUND
  Mesial temporal lobe epilepsy (mTLE) is characterized by hippocampal atrophy, decreased N-acetyl-aspartate, and a low N-acetyl-aspartate/total creatine ratio, often attributed to neuron loss and gliosis. Qualitative studies reported that N-acetyl-aspartate content was significantly lower in hippocampal sclerosis.
  
  
  OBJECTIVE
  It was proposed to measure the effects of neuron loss and gliosis on the hippocampal content of N-acetyl-aspartate, total creatine, and myo-inositol in mTLE.
  
  
  METHODS
  Twenty hippocampal specimens were obtained during temporal lobectomy and frozen quickly. Perchloric acid extracts of the small metabolites were prepared and analyzed by proton MRS at 11.75 T. Adjacent samples were used for cell counts.
  
  
  RESULTS
  There were no significant associations between hippocampal neuron loss and the cellular content of N-acetyl-aspartate, total creatine, or myo-inositol, despite more than a threefold difference in neuron loss and a twofold increase in glial density. Metabolite concentrations varied two- to fourfold. Variation in the cellular content of total creatine accounted for more than three-quarters of the rank-order variance of the N-acetyl-aspartate concentrations. There were no associations between myo-inositol and N-acetyl-aspartate or total creatine. Overall, mean N-acetyl-aspartate levels were below those reported by in vivo MRS studies of control subjects.
  
  
  CONCLUSIONS
  These data suggest that decreased N-acetyl-aspartate in mesial temporal lobe epilepsy reflects altered mitochondrial metabolism, not merely neuron loss or gliosis. It is hypothesized that the altered N-acetyl-aspartate and creatine metabolism could reflect mitochondrial dysfunction or proliferation of immature glial cells that could contribute to the epileptogenic state.
authors.affiliation: Department of Neurology, Yale University, New Haven, CT 06520-8018, USA. ognen.petroff@yale.edu
authors.forename: Ognen A C
authors.initials: OA
authors.lastname: Petroff
authors.forename: Laura D
authors.initials: LD
authors.lastname: Errante
authors.forename: Jung H
authors.initials: JH
authors.lastname: Kim
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Spencer
mesh_terms: D000293:Adolescent; D000328:Adult; D038481:Anterior Temporal Lobectomy; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis*; D001284:Atrophy; D003401:Creatine / Q000032:analysis*; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005911:Gliosis; D006624:Hippocampus / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D007294:Inositol / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology; D009474:Neurons / Q000737:chemistry; D012598:Sclerosis
chemical_list: D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine