Hypoxic Injury during Neonatal Development in Murine Brain: Correlation between In Vivo DTI Findings and Behavioral Assessment

Hypoxic Injury during Neonatal Development in Murine Brain: Correlation between In Vivo DTI Findings and Behavioral Assessment
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DOI:
10.1093/cercor/bhp068
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发表时间:
2009-12-01
期刊:
影响因子:
3.7
通讯作者:
Schwartz, Michael L.
Schwartz, Michael L.
中科院分区:
医学2区
文献类型:
--
作者:
Chahboune, Halima;Ment, Laura R.;Schwartz, Michael L.

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早产会导致严重的神经发育障碍。慢性亚致死缺氧(CSH)的新生儿啮齿动物模型模拟早产的影响,利用扩散张量成像的组织各向异性测量来表征长期缺氧的神经发育后果。胼胝体、扣带回和海马伞在成熟过程中显示出微妙但显着的缺氧诱导的变化(P15-P51)。在这些区域中,对照小鼠和 CSH 小鼠之间的各向异性差异在年龄较大时 (> P40) 最大。任何年龄的对照小鼠和 CSH 小鼠的体感皮层和尾壳核均未显示出显着差异。我们使用一般活动和认知测试来评估对照小鼠和 CSH 小鼠的形态变化的行为相关性。旷场任务显示,CSH 小鼠在成熟早期 (P16-P18) 具有更强的运动活性,而到了青春期 (P40-P45),对照小鼠和 CSH 小鼠之间的差异并不显着。这些结果可能与对照小鼠和 CSH 小鼠之间缺乏皮质和皮质下各向异性差异有关。成年后的空间延迟交替和自由游泳任务揭示了 CSH 小鼠空间记忆和行为偏侧性的持久损伤。这些差异可能与 CSH 小鼠海马和胼胝体连接性的各向异性减少有关。因此,CSH 小鼠表现出与低出生体重早产儿相似的发育和行为缺陷。
Preterm birth results in significant neurodevelopmental disability. A neonatal rodent model of chronic sublethal hypoxia (CSH), which mimics effects of preterm birth, was used to characterize neurodevelopmental consequences of prolonged exposure to hypoxia using tissue anisotropy measurements from diffusion tensor imaging. Corpus callosum, cingulum, and fimbria of the hippocampus revealed subtle, yet significant, hypoxia-induced modifications during maturation (P15-P51). Anisotropy differences between control and CSH mice were greatest at older ages (> P40) in these regions. Neither somatosensory cortex nor caudate putamen revealed significant differences between control and CSH mice at any age. We assessed control and CSH mice using tests of general activity and cognition for behavioral correlates of morphological changes. Open-field task revealed greater locomotor activity in CSH mice early in maturation (P16-P18), whereas by adolescence (P40-P45) differences between control and CSH mice were insignificant. These results may be associated with lack of cortical and subcortical anisotropy differences between control and CSH mice. Spatial-delayed alternation and free-swim tasks in adulthood revealed lasting impairments for CSH mice in spatial memory and behavioral laterality. These differences may correlate with anisotropy decreases in hippocampal and callosal connectivities of CSH mice. Thus, CSH mice revealed developmental and behavioral deficits that are similar to those observed in low birth weight preterm infants.