Brain injury and neurofunctional deficit in neonatal mice with hypoxic-ischemic encephalopathy
Brain injury and neurofunctional deficit in neonatal mice with hypoxic-ischemic encephalopathy
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DOI：
10.1016/s0166-4328(03)00146-3
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发表时间：
2003-10-17
影响因子：
2.7
通讯作者：
Pinsky, DJ
中科院分区：
文献类型：
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作者：
Ten, VS;Bradley-Moore, M;Pinsky, DJ
出生窒息是发育性运动和认知缺陷的主要原因。研究旨在建立一种可重复的围产期缺氧缺血性脑病（HIE）小鼠模型，该模型将允许对损伤进行解剖和神经功能量化。短期神经功能结果包括在单侧颈动脉结扎后吸入8%氧气24小时后7日龄小鼠幼崽的三种发育反射（翻正、悬崖厌恶和地向性）。脑梗死体积与缺氧持续时间有关，缺氧暴露时间较长（60分钟）与较短（30分钟）约为2.5倍（P = 0.001）。在HIE损伤后24小时评估的所有三种新生儿感觉运动反射与8周后对同一动物进行的导航学习和记忆水迷宫测试评估的长期神经功能显著相关。脑萎缩是该模型中HIE的延迟后果，也与水迷宫表现密切相关（r = 0.86, P = 0.002）。这些数据首次证明，小鼠新生儿感觉运动反射表现可以在围产期HIE急性期严格量化，不仅对脑损伤的解剖程度有很强的预测价值，而且对长期神经功能预后也有很强的预测价值。(C) 2003 Elsevier B.V.版权所有
Birth asphyxia accounts for the majority of developmental motor and cognitive deficits. Studies were undertaken to develop a reproducible murine model of perinatal hypoxic-ischemic encephalopathy (HIE) which would permit both anatomic and neurofunctional quantification of injury. Short-term neurofunctional outcomes consisted of three developmental reflexes (righting, cliff aversion and geotaxis) assessed in 7-day-old mouse pups 24 h after unilateral carotid artery ligation followed by inhalation of 8% oxygen. Cerebral infarct volume was dependent on duration of hypoxia, being approximate to2.5-fold greater with longer (60 min) versus shorter (30 min) hypoxia exposure (P = 0.001). All three sensorimotor neonatal reflexes assessed at 24 h after HIE injury correlated significantly with long-term neurofunction evaluated using a water-maze test of navigational learning and memory assessed 8 weeks later in the same animals. Cerebral atrophy, a delayed consequence of HIE in this model, also correlated strongly with water-maze performance (r = 0.86, P = 0.002). These data demonstrate for the first time that murine neonatal sensorimotor reflex performance can be rigorously quantified in the acute phase of perinatal HIE and has strong predictive value not only for anatomic extent of cerebral injury, but also for long-term neurofunctional outcome. (C) 2003 Elsevier B.V. All rights reserved.