Behavioral And Neuroanatomical Outcomes Of Early And Late Preterm Hypoxic-Ischemic Injury And The Neuroprotective Effects Of Whole-Body Hypothermia: An Animal Model

1 Behavioral and neuroanatomical outcomes of early and late preterm hypoxic ischemic injury and the neuroprotective effects of whole-body hypothermia: an animal model The overarching aims of this research were: first, to characterize the anatomical and behavioral effects of preterm hypoxic-ischemic (HI) injury in rodent models; and second, to explore the method of passively induced whole-body hypothermia as a neuroprotective intervention following HI. Clinical research of preterm injured infants has shown a large range of behavioral deficits, including delays in language learning, spatial and non-spatial memory, visual attention, and motor coordination. The current studies focused on these behavioral abnormalities, using HI rodent models. Specifically, we explored a model for early preterm HI (HI induced on postnatal day (P) 3 in rats), and compared it to the previous models we have used for late preterm HI (HI induced on P7), specifically using behavioral testing to characterize long-term outcomes. Additionally, the current studies sought to better characterize the language deficits associated with HI injury in humans, but using a rodent model to test the " magnocellular theory " of rapid auditory processing deficits. Research indicates that the use of cooling (both head-selective and whole body) has been shown to help reduce HI injury in both human populations and animal models. We set out to investigate how whole-body hypothermia might be used to ameliorate the behavioral deficits in an HI model, and specifically designed our focus on early preterm HI by using a P3 animal model. The overall goal of these studies was to expand upon knowledge regarding the behavioral and anatomical deficits associated with HI, and neuroprotective strategies following HI specifically, passively-induced whole-body hypothermia. 4 Introduction Hypoxic ischemic (HI) injuries result from compromised blood and/or oxygen flow to the brain. Such injuries can lead to mortality as well as long-term neurologic abnormalities in early preterm (gestational age < 34 weeks)/very low birth weight preterm (GA < 37 weeks) and full-term infants with birth complications (Fatemi et al., 2009, Volpe, 2001). Preterm/VLBW infants are vulnerable to HI injuries due to their fragile, underdeveloped cardiovascular systems and poor cerebral autoregulation.