Hill C A, Threlkeld S W, Fitch R H
University of Connecticut, Department of Psychology, Behavioral Neuroscience, 406 Babbidge Road, Unit 1020, Storrs, CT 06269, United States.
Int J Dev Neurosci. 2011 Oct;29(6):621-8. doi: 10.1016/j.ijdevneu.2011.07.009. Epub 2011 Jul 23.
Hypoxia ischemia (HI; reduced blood oxygenation and/or flow to the brain) represents one of the most common injuries for both term and preterm/very low birth weight (VLBW) infants. These children experience elevated incidence of cognitive and/or sensory processing disabilities, including language based learning disabilities. Clinical data also indicate more substantial long-term deficits for HI injured male babies as compared to HI injured females. Previously, we reported significant deficits in rapid auditory processing and spatial learning in male rats with postnatal day 1 (P1), P7, or P10 HI injury. We also showed sex differences in HI injured animals, with more severe deficits in males as compared to females. Given these findings, combined with extant clinical data, the current study sought to assess a putative role for perinatal testosterone in modulating behavioral outcome following early hypoxic-ischemic injury in rats. Male, female, and testosterone-propionate (TP) treated females were subjected to P7 HI or sham surgery, and subsequently (P30+) underwent a battery of auditory testing and water maze assessment. Results confirm previous reports of sex differences following HI, and add new findings of significantly worse performance in TP-treated HI females compared to vehicle treated HI females. Post mortem anatomic analyses showed consistent effects, with significant brain weight decreases seen in HI male and TP-treated HI females but not female HI or sham groups. Further neuromorphometric analysis of brain structures showed that HI male animals exhibited increased pathology relative to HI females as reflected in ventricular enlargement. Findings suggest that neonatal testosterone may act to enhance the deleterious consequences of early HI brain injury, as measured by both neuropathology and behavior.
缺氧缺血（HI；脑部血液氧合和/或血流量减少）是足月儿和早产/极低出生体重（VLBW）婴儿最常见的损伤之一。这些儿童出现认知和/或感觉处理障碍的发生率升高，包括基于语言的学习障碍。临床数据还表明，与HI损伤的女性相比，HI损伤的男婴长期缺陷更为严重。此前，我们报告了出生后第1天（P1）、P7或P10发生HI损伤的雄性大鼠在快速听觉处理和空间学习方面存在显著缺陷。我们还显示了HI损伤动物的性别差异，雄性比雌性存在更严重的缺陷。鉴于这些发现，结合现有的临床数据，本研究旨在评估围产期睾酮在调节大鼠早期缺氧缺血性损伤后行为结果中的假定作用。对雄性、雌性和经丙酸睾酮（TP）处理的雌性大鼠进行P7 HI或假手术，随后（P30+）进行一系列听觉测试和水迷宫评估。结果证实了先前关于HI后性别差异的报道，并增加了新的发现，即与接受载体处理的HI雌性大鼠相比，接受TP处理的HI雌性大鼠的表现明显更差。死后解剖分析显示出一致的结果，HI雄性和TP处理的HI雌性大鼠的脑重量显著降低，而雌性HI或假手术组则没有。对脑结构的进一步神经形态计量分析表明，与HI雌性大鼠相比，HI雄性动物表现出更多的病理变化，表现为脑室扩大。研究结果表明，通过神经病理学和行为测量，新生儿睾酮可能会加重早期HI脑损伤的有害后果。
