title: A novel mouse model of pediatric cardiac arrest and cardiopulmonary resuscitation reveals age-dependent neuronal sensitivities to ischemic injury.
abstract: BACKGROUND
  Pediatric sudden cardiac arrest (CA) is an unfortunate and devastating condition, often leading to poor neurologic outcomes. However, little experimental data on the pathophysiology of pediatric CA is currently available due to the scarcity of animal models.
  
  
  METHODS
  We developed a novel experimental model of pediatric cardiac arrest and cardiopulmonary resuscitation (CA/CPR) using postnatal day 20-25 mice. Adult (8-12 weeks) and pediatric (P20-25) mice were subjected to 6min CA/CPR. Hippocampal CA1 and striatal neuronal injury were quantified 3 days after resuscitation by hematoxylin and eosin (H&E) and Fluoro-Jade B staining, respectively.
  
  
  RESULTS
  Pediatric mice exhibited less neuronal injury in both CA1 hippocampal and striatal neurons compared to adult mice. Increasing ischemia time to 8 min CA/CPR resulted in an increase in hippocampal injury in pediatric mice, resulting in similar damage in adult and pediatric brains. In contrast, striatal injury in the pediatric brain following 6 or 8 min CA/CPR remained extremely low. As observed in adult mice, cardiac arrest causes delayed neuronal death in pediatric mice, with hippocampal CA1 neuronal damage maturing at 72 h after insult. Finally, mild therapeutic hypothermia reduced hippocampal CA1 neuronal injury after pediatric CA/CPR.
  
  
  CONCLUSIONS
  This is the first report of a cardiac arrest and CPR model of global cerebral ischemia in mice.
  
  
  CONCLUSIONS
  Therefore, the mouse pediatric CA/CPR model we developed is unique and will provide an important new tool to the research community for the study of pediatric brain injury.
authors.affiliation: Department of Pharmacology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO 80045, United States.
authors.forename: G
authors.initials: G
authors.lastname: Deng
authors.affiliation: Department of Anesthesiology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO 80045, United States.
authors.forename: J C
authors.initials: JC
authors.lastname: Yonchek
authors.affiliation: Department of Anesthesiology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO 80045, United States.
authors.forename: N
authors.initials: N
authors.lastname: Quillinan
authors.affiliation: Department of Anesthesiology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO 80045, United States.
authors.forename: F A
authors.initials: FA
authors.lastname: Strnad
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO 80045, United States.
authors.forename: J
authors.initials: J
authors.lastname: Exo
authors.affiliation: Department of Pharmacology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO 80045, United States; Department of Anesthesiology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO 80045, United States.
authors.forename: P S
authors.initials: PS
authors.lastname: Herson
authors.affiliation: Department of Pharmacology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO 80045, United States; Department of Anesthesiology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO 80045, United States. Electronic address: Richard.traystman@ucdenver.edu.
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
mesh_terms: D000375:Aging; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology* / Q000473:pathology* / Q000628:therapy; D056547:CA1 Region, Hippocampal / Q000254:growth & development / Q000473:pathology; D016887:Cardiopulmonary Resuscitation; D016923:Cell Death; D003342:Corpus Striatum / Q000254:growth & development / Q000473:pathology; D004195:Disease Models, Animal; D004801:Eosine Yellowish-(YS); D005452:Fluoresceins; D006323:Heart Arrest / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D006416:Hematoxylin; D007036:Hypothermia, Induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology; D010372:Pediatrics; D013997:Time Factors
chemical_list: D005452:Fluoresceins; C435731:fluoro jade; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin
keywords: Cardiac arrest; Global cerebral ischemia; Hypothermia; Juvenile; Pediatric