Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat: characterization of a translational preclinical model. Academic Article uri icon

Overview

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. CONCLUSION: 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.

publication date

  • May 21, 2015

Research

keywords

  • Brain
  • Hypothermia, Induced
  • Hypoxia-Ischemia, Brain

Identity

PubMed Central ID

  • PMC4543535

Scopus Document Identifier

  • 84939477302

Digital Object Identifier (DOI)

  • 10.1038/pr.2015.100

PubMed ID

  • 25996893

Additional Document Info

volume

  • 78

issue

  • 3