Neonatal rat hypoxia-ischemia: Long-term rescue of striatal neurons and motor skills by combined antioxidant-hypothermia treatment
Neonatal rat hypoxia-ischemia: Long-term rescue of striatal neurons and motor skills by combined antioxidant-hypothermia treatment
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DOI：
10.1111/j.1750-3639.2008.00146.x
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发表时间：
2008-07-01
期刊：
影响因子：
6.4
通讯作者：
Oorschot, Dorothy E.
中科院分区：
文献类型：
--
作者：
Hobbs, Catherine E.;Oorschot, Dorothy E.
围产期缺氧缺血可引起长期的神经和行为障碍。最近的多中心临床试验表明，出生后6小时内的中度低温可提供显著但不完全的保护。我们研究了抗氧化剂n -叔丁基-（2-巯基）-硝基酮（S-PBN）和中低温联合治疗对长期神经元损伤和行为障碍的影响。S-PBN或其稀释液于大鼠出生后第7天至第10天12小时给予。PN8诱导低氧缺血。缺氧后立即给予额外的S-PBN和6小时的中低温或额外的稀释液和6小时的常温。在缺氧缺血后1周和11周，测量编码右侧纹状体中存活的中棘神经元的绝对数量。在另一项实验中，研究人员对9至11周龄大鼠的熟练前爪能力进行了研究。正常的、未受伤的动物在9到11周大的时候也接受了运动技能测试。S-PBN联合中低温治疗对纹状体中棘神经元的短期和长期保护具有统计学意义。这种组合治疗也将精细运动技能保持在正常控制水平。令人印象深刻的组织学和功能保存表明，S-PBN和适度低温是一种安全而有吸引力的围产期缺氧缺血联合治疗方法。
Perinatal hypoxia-ischemia can cause long-term neurological and behavioral disability. Recent multicenter clinical trials suggest that moderate hypothermia, within 6 h of birth, offers significant yet incomplete protection. We investigated the effect of combined treatment with the antioxidant N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN) and moderate hypothermia on long-term neuronal injury and behavioral disability. S-PBN or its diluent was administered 12-hourly to rats from postnatal day (PN) 7 to 10. On PN8, hypoxia-ischemia was induced. Immediately post-hypoxia, additional S-PBN and 6 h of moderate hypothermia or additional diluent and 6 h of normothermia were administered. At 1 week, and at 11 weeks, after hypoxia-ischemia, the absolute number of surviving medium-spiny neurons was measured in the coded right striatum. In a separate experiment, skilled forepaw ability was investigated in coded 9- to 11-week-old rats. Normal, uninjured animals were also tested for motor skills at 9- to 11-weeks-of-age. The combination of S-PBN and moderate hypothermia provided statistically significant short- and long-term protection of the striatal medium-spiny neurons to normal control levels. This combinatorial treatment also preserved fine motor skills to normal control levels. The impressive histological and functional preservation suggests that S-PBN and moderate hypothermia is a safe and attractive combination therapy for perinatal hypoxia-ischemia.