title: Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain.
abstract: OBJECTIVE
  Early exposure to common anesthetic and sedative agents causes widespread brain cell degeneration and apoptosis in the developing rat brain, associated with persistent learning deficits in rats. This study was designed to determine whether the α2 adrenergic receptor agonist, dexmedetomidine, produces brain cell degeneration and apoptosis in postnatal day-7 rats in the same brain areas when compared to ketamine.
  
  
  METHODS
  Systemic saline, ketamine 20 mg/kg, or dexmedetomidine at 30 or 45 μg/kg were given six times to postnatal day 7 rats (n  =  6/group) every 90 min. Twenty-four hours after the initial injection, brain regions were processed and analyzed for cell degeneration using the silver stain and for apoptosis using activated caspase-3 immunohistochemistry.
  
  
  RESULTS
  Exposure to ketamine resulted in significant cellular degeneration and apoptosis in limbic brain regions, but nonsignificant changes in primary sensory brain regions. In contrast, dexmedetomidine produced significant cellular degeneration and apoptosis in primary sensory brain regions, but nonsignificant changes in limbic regions.
  
  
  CONCLUSIONS
  These data show that ketamine and dexmedetomidine result in anatomically distinct patterns of cell degeneration and apoptosis in the brains of 7-day-old rat pups. The meaning and the clinical significance of these findings remain to be established.
authors.affiliation: a Department of Anesthesiology , Tufts School of Medicine, Tufts Medical Center , Boston , MA , USA and.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pancaro
authors.affiliation: a Department of Anesthesiology , Tufts School of Medicine, Tufts Medical Center , Boston , MA , USA and.
authors.forename: B Scott
authors.initials: BS
authors.lastname: Segal
authors.affiliation: b Division of Movement and Rehabilitation Sciences , Department of Physical Therapy, Northeastern University , Boston , MA USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sikes
authors.affiliation: a Department of Anesthesiology , Tufts School of Medicine, Tufts Medical Center , Boston , MA , USA and.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Almeer
authors.affiliation: a Department of Anesthesiology , Tufts School of Medicine, Tufts Medical Center , Boston , MA , USA and.
authors.forename: Roman
authors.initials: R
authors.lastname: Schumann
authors.affiliation: a Department of Anesthesiology , Tufts School of Medicine, Tufts Medical Center , Boston , MA , USA and.
authors.forename: Ruben J
authors.initials: RJ
authors.lastname: Azocar
authors.affiliation: a Department of Anesthesiology , Tufts School of Medicine, Tufts Medical Center , Boston , MA , USA and.
authors.forename: James E
authors.initials: JE
authors.lastname: Marchand
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D016923:Cell Death; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects*; D065726:Limbic Lobe / Q000166:cytology / Q000187:drug effects*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000166:cytology / Q000187:drug effects*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000700:Analgesics; D020927:Dexmedetomidine; D007649:Ketamine
keywords: Anesthetic; apoptosis; developmental; dexmedetomidine; ketamine Neonatal; neurotoxicity; pediatric