Delayed administration of erythropoietin reducing hippocampal cell loss, enhancing angiogenesis and neurogenesis, and improving functional outcome following traumatic brain injury in rats: comparison of treatment with single and triple dose.
Delayed administration of erythropoietin reducing hippocampal cell loss, enhancing angiogenesis and neurogenesis, and improving functional outcome following traumatic brain injury in rats: comparison of treatment with single and triple dose.
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DOI：
10.3171/2009.9.jns09844
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发表时间：
2010-09
影响因子：
4.1
通讯作者：
Chopp M
中科院分区：
文献类型：
--
作者：
Xiong Y;Mahmood A;Meng Y;Zhang Y;Qu C;Schallert T;Chopp M
本研究旨在研究迟发性促红细胞生成素（EPO）治疗大鼠创伤性脑损伤（TBI）的效果，比较单剂量和三剂量。成年雄性Wistar大鼠随机分为以下组：1）假手术组（n = 6）; 2）TBI +生理盐水组（n = 6）; 3）TBI + EPOx 1组（n = 6）;和4）TBI + EPOx 3组（n = 7）。TBI是通过控制左侧顶叶皮质的皮质撞击而诱导的。在损伤后第1天（EPOx 1组）或第1、2和3天（EPOx 3组）腹腔内给予EPO（5，000 U/kg）或生理盐水。采用改良的神经功能严重程度评分（mNSS）、足错和Morris水迷宫试验评估神经功能。损伤后35天处死动物，并对脑切片进行免疫组织化学染色。与生理盐水治疗相比，EPOx 1和EPOx 3组中的EPO治疗显著减少海马细胞损失，增强损伤皮层和海马中的血管生成和神经发生，并显著改善神经功能结局。与EPOx 1组相比，EPOx 3组表现出显著改善的功能和组织学结局。这些数据表明，延迟创伤后给予EPO显着改善组织学和长期功能的结果在大鼠TBI后。三次剂量的延迟EPO治疗在大鼠中表现出更好的组织学和功能结果，尽管与盐水治疗相比，单次剂量的EPO提供了实质性益处。
This study was designed to investigate delayed erythropoietin (EPO) treatment for traumatic brain injury (TBI) in rats comparing efficacy of a single dose with triple doses. Young adult male Wistar rats were randomly divided into the following groups: 1) Sham group (n = 6); 2) TBI + Saline group (n = 6); 3) TBI + EPOx1 group (n = 6); and 4) TBI + EPOx3 group (n = 7). TBI was induced by controlled cortical impact over the left parietal cortex. EPO (5,000 U/kg) or saline was administered intraperitoneally at 1 day (EPOx1 group) or at days 1, 2, and 3 (EPOx3 group) post injury. Neurological function was assessed using a modified neurological severity score (mNSS), footfault and Morris water maze tests. Animals were sacrificed 35 days after injury and brain sections stained for immunohistochemistry. Compared to the saline treatment, EPO treatment in both the EPOx1 and EPOx3 groups significantly reduced hippocampal cell loss, enhanced angiogenesis and neurogenesis in the injured cortex and hippocampus, and significantly improved neurological functional outcome. The EPOx3 group exhibited significantly improved functional and histological outcomes compared with the EPOx1 group. These data demonstrate that delayed posttraumatic administration of EPO significantly improves histological and long-term functional outcomes in rats after TBI. The triple doses of delayed EPO treatment exhibit better histological and functional outcomes in rats although a single dose of EPO provides substantial benefits compared to saline treatment.