title: Subunit composition of glutamate and gamma-aminobutyric acid receptors in status epilepticus.
abstract: OBJECTIVE
  To describe the subunit composition of glutamate and gamma-aminobutyric acid (GABA) receptors in brain tissue from patients with different types of status epilepticus.
  
  
  METHODS
  The subunit composition of glutamate and GABA receptors was analyzed in: (1) surgical brain samples from three patients with refractory convulsive status epilepticus, three patients with electrical status epilepticus in sleep, and six patients with refractory epilepsy, and (2) brain autopsy samples from four controls who died without neurological disorders. Subunit expression was quantified with Western blotting and messenger ribonucleic acid (mRNA) expression was quantified with reverse polymerase chain reaction.
  
  
  RESULTS
  Western blot analysis demonstrated the following patterns (as compared to controls): (1) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors: elevated GluA1/GluA2 ratio in electrical status epilepticus in sleep (465%±119) and refractory epilepsy (329%±125; p<0.01); (2) N-methyl-d-aspartate (NMDA) receptors: increased GluN2B/GluN2A ratio in electrical status epilepticus in sleep (3682%±1000) and refractory convulsive status epilepticus (3520%±751; p<0.05); (3) GABA receptors: elevated α2/α1 ratio in refractory epilepsy (321%±138; p<0.05) and refractory convulsive status epilepticus (346%±74; p<0.05); and (4) patients with underlying malformation of cortical development had increased ratios in GluA1/GluA2 (382%±149; p<0.01), GluN2B/GluN2A (3321%±1581; p<0.05) and α2/α1 (303%±86; p<0.01). Quantification of mRNA demonstrated an elevated GABRA2/GABRA1 ratio in refractory epilepsy (712; p<0.05) as compared to controls.
  
  
  CONCLUSIONS
  The subunit composition of glutamate and GABA receptors in patients with status epilepticus mirrors that found in animal models of refractory status epilepticus and may promote self-sustaining seizures. Receptor subunit changes may provide additional targets for improved treatment.
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: tobias.loddenkemper@childrens.harvard.edu.
authors.forename: Tobias
authors.initials: T
authors.lastname: Loddenkemper
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, New York University Comprehensive Epilepsy Center, New York University Langone Medical Center, New York University School of Medicine, New York, NY, USA.
authors.forename: Delia M
authors.initials: DM
authors.lastname: Talos
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Cleary
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Annelise
authors.initials: A
authors.lastname: Joseph
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Child Neurology, Hospital Sant Joan de Déu, Universidad de Barcelona, Barcelona, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Sánchez Fernández
authors.affiliation: Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Alexopoulos
authors.affiliation: Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Kotagal
authors.affiliation: Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Imad
authors.initials: I
authors.lastname: Najm
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Jensen
mesh_terms: D000293:Adolescent; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D021122:Protein Subunits / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D013226:Status Epilepticus / Q000378:metabolism*; D055815:Young Adult
chemical_list: D021122:Protein Subunits; D018079:Receptors, GABA; D017470:Receptors, Glutamate
keywords: Children; Epilepsy; Receptor subunit composition; Refractory status epilepticus; Therapy