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This preparation models brain injury seen in premature infants (gestational age (GA) 32\u201335 weeks) based on shared neurodevelopmental markers at time of insult, coupled with similar neuropathologic sequelae (Rice et al., 1981; Workman et al., 2013). Clinically, HI insult during this window is associated with poor outcomes that include attention deficit hyperactivity disorder (ADHD), motor coordination deficits, spatial memory deficits, and language\/learning disabilities. To assess therapies that might offer translational potential for improved outcomes, we used a P6 HI rat model to measure the behavioral and neuroanatomical effects of two prospective preterm neuroprotective treatments \u2013 hypothermia and caffeine. Hypothermia (aka \u201ccooling\u201d) is an approved and moderately efficacious intervention therapy for fullterm infants with perinatal hypoxic\u2010ischemic (HI) injury, but is not currently approved for preterm use. Caffeine is a respiratory stimulant used during removal of infants from ventilation but has shown surprising long\u2010term benefits, leading to consideration as a therapy for HI of prematurity. Current findings support caffeine as a preterm neuroprotectant; treatment significantly improved some behavioral outcomes in a P6 HI rat model and partially rescued neuropathology. Hypothermia treatment (involving core temperature reduction by 4\u202f\u00b0C for 5\u202fh), conversely, was found to be largely ineffective and even deleterious for some measures in both HI and sham rats. These results have important implications for therapeutic intervention in at\u2010risk preterm populations, and promote caution in the application of hypothermia protocols to at\u2010risk premature infants without further research.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2018.02.001","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T16:26:23Z","timestamp":1519403183000},"page":"46-55","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Behavioral and neuroanatomical outcomes in a rat model of preterm hypoxic\u2010ischemic brain Injury: Effects of caffeine and hypothermia"],"prefix":"10.1002","volume":"70","author":[{"given":"Molly","family":"Potter","sequence":"first","affiliation":[{"name":"University of Connecticut Health Center, School of Medicine Farmington CT United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Rosenkrantz","sequence":"additional","affiliation":[{"name":"University of Connecticut Health Center Dept. of Pediatrics\/Neonatology Farmington CT United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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