Research Article Effects of Sex and Mild Intrainsult Hypothermia on Neuropathology and Neural Reorganization following Neonatal Hypoxic Ischemic Brain Injury in Rats Amanda L. Smith, 1 Ted S. Rosenkrantz, 2 and R. Holly Fitch 1 1 Department of Psychology, Behavioral Neuroscience Division, Te University of Connecticut, 406 Babbidge Road, Storrs, CT 06269, USA 2 Department of Pediatrics/Neonatology, Te University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA Correspondence should be addressed to Amanda L. Smith; amanda.l.smith@uconn.edu Received 4 November 2015; Revised 8 January 2016; Accepted 31 January 2016 Academic Editor: Mariya Hristova Copyright © 2016 Amanda L. Smith et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hypoxia ischemia (HI) is a recognized risk factor among late-preterm infants, with HI events leading to varied neuropathology and cognitive/behavioral defcits. Studies suggest a sex diference in the incidence of HI and in the severity of subsequent behavioral defcits (with better outcomes in females). Mechanisms of a female advantage remain unknown but could involve sex-specifc patterns of compensation to injury. Neuroprotective hypothermia is also used to ameliorate HI damage and attenuate behavioral defcits. Tough currently prescribed only for HI in term infants, cooling has potential intrainsult applications to high-risk late- preterm infants as well. To address this important clinical issue, we conducted a study using male and female rats with a postnatal (P) day 7 HI injury induced under normothermic and hypothermic conditions. Te current study reports patterns of neuropathology evident in postmortem tissue. Results showed a potent beneft of intrainsult hypothermia that was comparable for both sexes. Findings also show surprisingly diferent patterns of compensation in the contralateral hemisphere, with increases in hippocampal thickness in HI females contrasting reduced thickness in HI males. Findings provide a framework for future research to compare and contrast mechanisms of neuroprotection and postinjury plasticity in both sexes following a late-preterm HI insult. 1. Introduction A common brain insult, associated with preterm birth (<37 weeks of gestational age (GA); [1, 2]), very low birth weight (VLBW; <1500 grams), and term birth complications (e.g., cord prolapse and cord asphyxia [3, 4]), involves a drop in blood and/or oxygen fow to the brain (hypoxia ischemia; HI). In preterm infants, the vulnerability of the developing brain plays a pivotal role in the etiology of HI, with fragility of the neurovascular system leading to increased risk of hemorrhagic and nonhemorrhagic (ischemic) brain injuries [1, 3, 5–7]. In turn, contemporary premature cohorts ofen exhibit mild/difuse forms of injury that include grey matter damage in areas such as the cortex and hippocampus and white-matter tissue loss characteristic of difuse periventricu- lar leukomalacia (PVL; e.g., tissue loss in corpus callosum and internal capsule [8, 9]). While the brain is highly vulnerable in the preterm infant, the plasticity of the developing brain simultaneously provides a prime target for neural reorganiza- tion, prompting further study of brain injuries specifc to this unique population of infants. Compensatory mechanisms could ofset severe tissue loss (as would be seen in adults with comparable HI events) and instead lead to more subtle anomalies. Tough obvious sex diferences characterize development (i.e., delays in male fetal development that may lead to pro- longed vulnerability to brain injury in the neonatal period) and are also reported in behavioral outcomes following an HI insult (in both clinical studies and animal models [10– 15]), clinicians currently implement identical neuroprotective regimens (hypothermia or “cooling”) for both male and female term infants with hypoxic ischemic encephalopathy Hindawi Publishing Corporation Neural Plasticity Volume 2016, Article ID 2585230, 11 pages http://dx.doi.org/10.1155/2016/2585230