Behavioral and neuroanatomical outcomes in a rat model of preterm hypoxic-ischemic brain Injury: Effects of caffeine and hypothermia.The current study investigated behavioral and post mortem neuroanatomical outcomes in Wistar rats with a neonatal hypoxic-ischemic (HI) brain injury induced on postnatal day 6 (P6; Rice-Vannucci HI method; Rice et al., 1981).  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 - hypothermia and caffeine.  Hypothermia (aka "cooling") is an approved and moderately efficacious intervention therapy for fullterm infants with perinatal hypoxic-ischemic (HI) injury, but is not currently approved for preterm use.  Hypothermia treatment (involving core temperature reduction by 4 °C for 5 h), 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-risk preterm populations, and promote caution in the application of hypothermia protocols to at-risk premature infants without further research.
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