title: Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat: characterization of a translational preclinical model.
abstract: BACKGROUND
  Hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity in survivors. Therapeutic hypothermia (TH) is the only available intervention, but the protection is incomplete. Preclinical studies of HIE/TH in the rodent have relied on the postnatal day (P) 7 rat whose brain approximates a 32-36 wk gestation infant, less relevant for these studies. We propose that HIE and TH in the term-equivalent P10 rat will be more translational.
  
  
  METHODS
  P10-11 rat pups were subjected to unilateral hypoxia-ischemia (HI) and 4 h recovery in normothermic (N) or hypothermic (TH) conditions. Brain damage was assessed longitudinally at 24 h, 2 wk, and 12 wk. Motor function was assessed with the beam walk; recognition memory was measured by novel object recognition.
  
  
  RESULTS
  Neuroprotection with TH was apparent at 2 and 12 wk in both moderately and severely damaged animals. TH improved motor function in moderate, but not severe, damage. Impaired object recognition occurred with severe damage with no evidence of protection of TH.
  
  
  CONCLUSIONS
  This adaptation of the immature rat model of HI provides a reproducible platform to further study HIE/TH in which individual animals are followed up longitudinally to provide a useful translational preclinical model.
authors.affiliation: Department of Pediatrics, Weill Cornell Medical College, New York, New York.
authors.forename: Shyama D
authors.initials: SD
authors.lastname: Patel
authors.affiliation: 1] Department of Pediatrics, Weill Cornell Medical College, New York, New York [2] Department of Pediatrics, Baylor University Medical Center, Dallas, Texas.
authors.forename: Leslie
authors.initials: L
authors.lastname: Pierce
authors.affiliation: Department of Pediatrics, Weill Cornell Medical College, New York, New York.
authors.forename: Amber
authors.initials: A
authors.lastname: Ciardiello
authors.affiliation: Department of Pediatrics, Weill Cornell Medical College, New York, New York.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hutton
authors.affiliation: New York State Psychiatric Institute, New York, New York.
authors.forename: Samuel
authors.initials: S
authors.lastname: Paskewitz
authors.affiliation: Citigroup Biomedical Imaging Center, Weill Cornell Medical College, New York, New York.
authors.forename: Eric
authors.initials: E
authors.lastname: Aronowitz
authors.affiliation: 1] Citigroup Biomedical Imaging Center, Weill Cornell Medical College, New York, New York [2] Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Henning U
authors.initials: HU
authors.lastname: Voss
authors.affiliation: 1] New York State Psychiatric Institute, New York, New York [2] Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Holly
authors.initials: H
authors.lastname: Moore
authors.affiliation: Department of Pediatrics, Weill Cornell Medical College, New York, New York.
authors.forename: Susan J
authors.identifier: 0000000295861561
authors.initials: SJ
authors.lastname: Vannucci
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D007036:Hypothermia, Induced / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D007858:Learning; D008279:Magnetic Resonance Imaging; D008297:Male; D023421:Models, Animal; D009048:Motor Skills; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D047929:Term Birth; D013997:Time Factors; D057170:Translational Research, Biomedical