title: Metabolic injury in a variable rat model of post-status epilepticus.
abstract: In vivo studies of epilepsy typically use prolonged status epilepticus to generate recurrent seizures. However, reports on variable status duration have found discrete differences in injury after 40-50 min of seizures, suggesting a pathophysiologic sensitivity to seizure duration. In this report we take a multivariate cluster analysis to study a short duration status epilepticus model using in vivo 7T magnetic resonance spectroscopy (MRS) and histologic evaluation.
  
  
  
  The Hellier Dudek model was applied with 45 min of status epilepticus after which the animals were imaged twice, at 3 days and 3 weeks post-status epilepticus. Single voxel point resolved spectroscopy (PRESS) MRS was used to acquire data from the dentate gyrus and CA3 region of the hippocampus, assessing metabolite ratios to total creatine (tCr). In a subset of animals after the second imaging study, brains were analyzed histologically by Nissl staining.
  
  
  
  A hierarchical cluster analysis performed on the 3-day data from 21 kainate-treated animals (dentate gyrus voxel) segregated into two clusters, denoted by KM (more injured, n = 6) and KL (less injured, n = 15). Although there was no difference in kainate dosing or seizure count between them, the metabolic pattern of injury was different. The KM group displayed the largest significant changes in neuronal and glial parameters; the KL group displayed milder but significant changes. At 3 weeks, the KL group returned to normal compared to controls, whereas the KM group persisted with depressed N-acetyl aspartate (NAA)/tCr, glutamate/tCr, and increased inositol/tCr and glutamine/tCr. The classification was also consistent with subsequent histologic patterns at 3 weeks.
  
  
  
  Although a short status period might be expected to generate a continuous distribution of metabolic injury, these data show that the short Hellier Dudek model appears to generate two levels of injury. The changes seen in segregated groups persisted into 3 weeks, and can be interpreted according to neuronal and glial biomarkers consistent with histology results.
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
authors.forename: Patrice S
authors.initials: PS
authors.lastname: Pearce
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
authors.forename: Yijen
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Rapuano
authors.affiliation: Department of Neurology, Allegheny Singer Research Institute, Pittsburgh, Pennsylvania, U.S.A.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Kelly
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Nihal
authors.initials: N
authors.lastname: de Lanerolle
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.|Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
authors.forename: Jullie W
authors.initials: JW
authors.lastname: Pan
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D016000:Cluster Analysis; D003401:Creatine / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008659:Metabolic Diseases / Q000000981:diagnostic imaging / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine; D007608:Kainic Acid
keywords: Glutamate; Kainate; Status epilepticus