title: Widespread neuronal injury in a model of cholinergic status epilepticus in postnatal day 7 rat pups.
abstract: OBJECTIVE
  Status Epilepticus (SE) is common in neonates and infants, and is associated with neuronal injury and adverse developmental outcomes. However, the role of SE in this injury is uncertain. Until now, we have lacked an animal model in which seizures result in neuronal injury in rodent models at ages below postnatal day 12 (P12) unless seizures are combined with inflammatory stressors.
  
  
  METHODS
  We induced SE with high-dose lithium and pilocarpine in P7 rats, which are developmentally close to human neonates. Several EEG measures and O2 saturation were recorded during the 6h following initiation of SE. We assessed neuronal injury at 6 and 24h post-SE onset using Fluoro-Jade B staining (FJB) and caspase-3a immunoreactivity (IR).
  
  
  RESULTS
  EEGs showed continuous polyspikes activity for 54.3 ± 6.7 min, while O2 saturation showed no significant hypoxemia. By 24h after SE onset, significant neuronal injury was observed in CA1/subiculum, CA3, dentate gyrus, thalamus, neocortex, amygdala, piriform cortex, lateral entorhinal cortex, hypothalamus, caudate putamen, globus pallidus, ventral pallidum, and nucleus accumbens. At 24h post-SE, caspase-3a IR was significantly increased in CA1/subiculum, thalamus, and neocortex compared to sham, and caspase-3a IR neurons had fragmented nuclei, suggesting that SE triggered an irreversible form of cell injury.
  
  
  CONCLUSIONS
  In conclusion, we have developed a model of cholinergic SE in P7 rat pups, which combines high survival (69.9% survival at 24h) and widespread brain injury. These studies suggest that the immature brain is vulnerable to severe forms of SE.
authors.affiliation: Epilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Torolira
authors.affiliation: Epilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Lucie
authors.initials: L
authors.lastname: Suchomelova
authors.affiliation: Epilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Claude G
authors.initials: CG
authors.lastname: Wasterlain
authors.affiliation: Epilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: jniquet@ucla.edu.
authors.forename: Jerome
authors.initials: J
authors.lastname: Niquet
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D000069280:Electrocorticography; D004569:Electroencephalography; D005260:Female; D007150:Immunohistochemistry; D018020:Lithium Compounds; D008297:Male; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D010862:Pilocarpine; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D018020:Lithium Compounds; D010862:Pilocarpine; C505410:Casp3 protein, rat; D053148:Caspase 3; D010100:Oxygen
keywords: Active caspase-3; Fluoro–Jade B; Hippocampus; Immature brain; Neonate; Seizures