RESEARCH ARTICLE Hypoxia-Ischemia and Therapeutic Hypothermia in the Neonatal Mouse Brain – A Longitudinal

Therapeutic hypothermia is standard of care for infants with hypoxic ischemic encephalopa-thy. Murine models of hypoxic-ischemic injury exist; however, a well-established mouse model of therapeutic hypothermia following hypoxic-ischemic injury is lacking. The goal of this study was to develop a full-term-equivalent murine model of therapeutic hypothermia after hypoxia-ischemia and examine magnetic resonance imaging, behavior, and histology in a region and sex specific manner. Hypoxic-ischemic injury was induced at postnatal day 10 in C57BL6 mice using a modified Vannucci model. Mice were randomized to control, hy-pothermia (31˚C for 4h), or normothermia (36˚C) following hypoxic-ischemic injury and strat-ified by sex. T2-weighted magnetic resonance imaging was obtained at postnatal day 18 and 30 and regional and total cerebral and cerebellar volumes measured. Behavioral as-sessments were performed on postnatal day 14, 21, and 28. On postnatal day 18, normo-thermic mice had smaller cerebral volumes (p< 0.001 vs. controls and p = 0.009 vs. hypothermia), while at postnatal day 30 both injured groups had smaller volumes than con-trols. When stratified by sex, only normothermia treated male mice had smaller cerebral vol