The contribution of intermittent hypoxemia to late neurological handicap in mice with hyperoxia-induced lung injury
The contribution of intermittent hypoxemia to late neurological handicap in mice with hyperoxia-induced lung injury
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DOI：
10.1159/000100086
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发表时间：
2007-01-01
期刊：
影响因子：
2.5
通讯作者：
Ten, Vadim S.
中科院分区：
文献类型：
--
作者：
Ratner, Veniamin;Kishkurno, Sergey V.;Ten, Vadim S.
许多人认为，支气管肺发育不良(BPD)是早产儿神经发育不良的独立危险因素。然而，患有BPD的婴儿会经历间歇性低氧发作。这项研究旨在确定与BPD相关的间歇性低氧应激是否有助于神经功能障碍的发展。新生小鼠暴露于高氧(65%O-2)4周后建立BPD模型。用动脉血气、肺力学和组织病理学来确定肺损伤的程度。在高氧性肺损伤的不同阶段，给予小鼠短暂(10min/d)和间歇性(10d)低氧应激(8%O-2)。出生8周后，用水迷宫和转杆实验评估神经功能，然后用Nissl、溴脱氧尿苷和caspase-3免疫组织化学染色进行脑组织形态分析。将数据与幼稚的常氧低氧小鼠和那些只暴露于高氧或间歇性低氧的小鼠进行比较。BPD组小鼠在短暂/间歇低氧状态下的航行记忆表现明显低于常氧小鼠和未处于间歇低氧状态的BPD组小鼠。这些小鼠的神经功能障碍与脑重量显著减少和脑caspase-3表达增加有关。我们的结果表明，间歇性低氧与高氧诱导的肺损伤有关，而不是肺损伤本身，导致BPD新生小鼠显著的神经功能障碍。版权所有(C)2007 S.Karger AG，巴塞尔。
Bronchopulmonary dysplasia ( BPD) is considered by many to be an independent risk factor for poor neurodevelopment in premature infants. However, infants with BPD experience intermittent hypoxic episodes. This study was undertaken to determine whether intermittent hypoxic stress associated with BPD contributes to the development of neurological deficit. The model of BPD was produced in neonatal mice by exposure to hyperoxia ( 65% O-2) for 4 weeks. Arterial blood gases, pulmonary mechanics, and histopathology were used to define the degree of lung injury. The mice were subjected to brief ( 10 min/day) and intermittent ( 10 days) hypoxic stress ( 8% O-2) at different stages of the development of hyperoxia- induced lung injury. At 8 weeks of life, the neurofunction was assessed by water maze and rota-rod tests followed by cerebral morphological analysis using Nissl, bromodeoxyuridine, and caspase- 3 immunostaining. Data were compared to naive normoxic littermates and those mice that were exposed only to hyperoxia or intermittent hypoxia alone. Mice with BPD subjected to brief/ intermittent hypoxia demonstrated a significantly poorer navigational memory performance as compared with normoxic mice and mice with BPD that were not subjected to intermittent hypoxia. The neurofunctional handicap in these mice was associated with significantly decreased brain weight and increased cerebral expression of caspase- 3. Our results suggest that intermittent hypoxia associated with hyperoxia-induced lung injury, but not lung injury itself, results in significant neurological handicap in neonatal mice with BPD. Copyright (c) 2007 S. Karger AG, Basel.