Effects of combination therapy using hypothermia and erythropoietin in a rat model of neonatal hypoxia-ischemia.

Effects of combination therapy using hypothermia and erythropoietin in a rat model of neonatal hypoxia-ischemia.
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在新生儿缺氧 - 缺血症的大鼠模型中,使用体温过低和红细胞生成素组合疗法的影响。

DOI:
10.1038/pr.2012.138
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发表时间:
2013-01
期刊:
影响因子:
3.6
通讯作者:
Ferriero, Donna M.
Ferriero, Donna M.
中科院分区:
医学3区
文献类型:
--
作者:
Fang, Annie Y.;Gonzalez, Fernando F.;Sheldon, R. Ann;Ferriero, Donna M.

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对发育中的脑的缺氧缺血(HI)损伤仍然是发病率的主要原因。低温是有效的,但不能提供完全的神经保护,这促使人们寻找辅助疗法。促红细胞生成素(EPO)已被证明在几种新生儿HI模型中是有益的。本研究探讨了低温联合促红细胞生成素治疗新生大鼠缺氧缺血性脑病的效果。将出生后第7天的大鼠随机分为4组:不治疗组、单纯亚低温组、单纯促红细胞生成素组、亚低温+促红细胞生成素组。EPO(1000U/kg)分3次给药,分别于缺氧缺血后即刻、24 h和1wk后给药。低温包括全身降温8h,分别于伤后2wk和6wk通过柱体抬高试验评价感觉运动功能,以损伤评分评价脑损伤。未遭受HI的假处理动物也被研究。试验组之间的差异,除了EPO治疗对男性组织病理学结果的影响外,没有统计学意义,联合治疗没有不良反应。无论是低温治疗还是联合治疗,均未观察到明显的益处。未来的研究可能需要更年长的动物,更广泛的功能测试,以及创伤后严重程度的评估,以确定只有中度损伤的动物进行靶向治疗。
Hypoxic–ischemic (HI) injury to the developing brain remains a major cause of morbidity. Hypothermia is effective but does not provide complete neuroprotection, prompting a search for adjunctive therapies. Erythropoietin (Epo) has been shown to be beneficial in several models of neonatal HI. This study examines combination hypothermia and treatment with erythropoietin in neonatal rat HI. Rats at postnatal day 7 were subjected to HI (Vannucci model) and randomized into four groups: no treatment, hypothermia alone, Epo alone, or hypothermia and Epo. Epo (1,000 U/kg) was administered in three doses: immediately following HI, and 24 h and 1 wk later. Hypothermia consisted of whole-body cooling for 8 h. At 2 and 6 wk following HI, sensorimotor function was assessed via cylinder-rearing test and brain damage by injury scoring. Sham-treated animals not subjected to HI were also studied. Differences between experimental groups, except for Epo treatment on histopathological outcome in males, were not statistically significant, and combined therapy had no adverse effects. No significant benefit was observed from treatment with either hypothermia or combination therapy. Future studies may require older animals, a wider range of functional assays, and postinsult assessment of injury severity to identify only moderately damaged animals for targeted therapy.
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