Docosahexaenoic Acid Augments Hypothermic Neuroprotection in a Neonatal Rat Asphyxia Model
Docosahexaenoic Acid Augments Hypothermic Neuroprotection in a Neonatal Rat Asphyxia Model
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DOI：
10.1159/000351011
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发表时间：
2013-01-01
期刊：
影响因子：
2.5
通讯作者：
Silverstein, Faye S.
中科院分区：
文献类型：
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作者：
Berman, Deborah R.;Mozurkewich, Ellen;Silverstein, Faye S.
背景：新生大鼠缺氧缺血(HI)后早期应用omega-3脂肪酸二十二碳六烯酸(DHA)可改善感觉运动功能，但不能减轻脑损伤。目的：探讨新生儿窒息脑损伤在低温治疗的基础上加用DHA能否减轻缺氧缺血后的损伤和感觉运动障碍。方法：7日龄(P7)大鼠右侧颈总动脉结扎后给予90min的8%O2暴露。15分钟后，给幼鼠注射DHA 2.5 mg/kg(与25%白蛋白络合)或等量白蛋白。恢复1小时后，给幼鼠降温(3小时，30摄氏度)。在P14时对感觉运动和病理结果进行初步评估。在随后的实验中，在P14、P21和P28评估感觉运动功能；在P28评估组织病理学。结果：在P14时，DHA+亚低温组动物的左前爪功能评分(正常：20/20)接近正常(平均+/-SD19.7+/-0.7DHA+亚低温组12.7+/-3.5白蛋白+亚低温组，p=0.0001)，脑损伤减轻(平均+/-SD右脑损害38+/-17%与白蛋白+亚低温组56+/-15%，p=0.003)。直到P28，三项感觉运动功能指标的显著改善和脑损伤的减少都很明显。结论：与单纯应用DHA治疗不同，DHA+亚低温治疗可持续改善新生儿HI后的功能，减少脑损伤。版权所有(C)2013 S.Karger AG，巴塞尔
Background: In neonatal rats, early post-hypoxia-ischemia (HI) administration of the omega-3 fatty acid docosahexaenoic acid (DHA) improves sensorimotor function, but does not attenuate brain damage. Objective: To determine if DHA administration in addition to hypothermia, now standard care for neonatal asphyxial brain injury, attenuates post-HI damage and sensorimotor deficits. Methods: Seven-day-old (P7) rats underwent right carotid ligation followed by 90 min of 8% O-2 exposure. Fifteen minutes later, pups received injections of DHA 2.5 mg/kg (complexed to 25% albumin) or equal volumes of albumin. After a 1-hour recovery, pups were cooled (3 h, 30 degrees C). Sensorimotor and pathology outcomes were initially evaluated on P14. In subsequent experiments, sensorimotor function was evaluated on P14, P21, and P28; histopathology was assessed on P28. Results: At P14, left forepaw function scores (normal: 20/20) were near normal in DHA + hypothermia-treated animals (mean +/- SD 19.7 +/- 0.7 DHA + hypothermia vs. 12.7 +/- 3.5 albumin + hypothermia, p < 0.0001) and brain damage was reduced (mean +/- SD right hemisphere damage 38 +/- 17% with DHA + hypothermia vs. 56 +/- 15% with albumin + hypothermia, p = 0.003). Substantial improvements on three sensorimotor function measures and reduced brain damage were evident up to P28. Conclusion: Unlike post-HI treatment with DHA alone, treatment with DHA + hypothermia produced both sustained functional improvement and reduced brain damage after neonatal HI. Copyright (C) 2013 S. Karger AG, Basel