Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin
Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin
复制标题
DOI：
10.3171/jns-07/08/0392
复制
发表时间：
2007-08-01
影响因子：
4.1
通讯作者：
Chopp, Michael
中科院分区：
文献类型：
--
作者：
Mahmood, Asim;Lu, Dunyue;Chopp, Michael
Object.本研究旨在探讨重组促红细胞生成素（EPO）和氨甲酰化促红细胞生成素（CEPO）对大鼠创伤性脑损伤（TBI）后的神经保护作用。60只成年雄性Wistar大鼠用控制性皮质撞击损伤，然后腹腔内注射EPO、CEPO或安慰剂（磷酸盐缓冲盐水）。这些注射在TBI后6或24小时进行。为了标记新再生的细胞，在TBI后腹膜内注射溴脱氧尿苷14天。在第1、2、3、7、14和35天采集血样，以测量红细胞压积。使用Morris水迷宫测试空间学习。TBI后35天处死所有大鼠。脑组织切片行免疫组化染色，酶联免疫吸附试验测定脑源性神经营养因子（BDNF）。在TBI后6或24小时用EPO或CEPO治疗的大鼠中观察到空间学习的统计学显著改善（p < 0.05）; EPO和CEPO的效果没有差异。此外，这些药物在两个时间点都同样有效地增加了齿状回内新增殖细胞的数量。在TBI后6或24小时，在用两种EPO衍生物治疗的动物中观察到BDNF表达的统计学显著增加。EPO治疗后48 h、1周和2周，红细胞压积显著升高，而CEPO治疗后红细胞压积无明显变化。这些数据表明，在所使用的剂量下，EPO和CEPO在增强TBI后的空间学习和促进神经可塑性方面同样有效。
Object. This study was designed to investigate the neuroprotective properties of recombinant erythropoietin (EPO) and carbamylated erythropoietin (CEPO) administered following traumatic brain injury (TBI) in rats.Methods. Sixty adult male Wistar rats were injured with controlled cortical impact, and then EPO, CEPO, or a placebo (phosphate-buffered saline) was injected intraperitoneally. These injections were performed either 6 or 24 hours after TBI. To label newly regenerating cells, bromodeoxyuridine was injected intraperitoneally for 14 days after TBI. Blood samples were obtained on Days 1, 2, 3, 7, 14, and 35 to measure hematocrit. Spatial learning was tested using the Morris water maze. All rats were killed 35 days after TBI. Brain sections were immunostained as well as processed for the enzyme-linked immunosorbent assay to measure brain-detived neurotrophic factor (BDNF).Results. A statistically significant improvement in spatial learning was seen in rats treated with either EPO or CEPO 6 or 24 hours after TBI (p < 0.05); there was no difference in the effects of EPO and CEPO. Also, these drugs were equally effective in increasing the number of newly proliferating cells within the dentate gyrus at both time points. A statistically significant increase in BDNF expression was seen in animals treated with both EPO derivatives at 6 or 24 hours after TBI. Systemic hematocrit was significantly increased at 48 hours and 1 and 2 weeks after treatment with EPO but not with CEPO.Conclusions. These data demonstrate that at the doses used, EPO and CEPO are equally effective in enhancing spatial learning and promoting neural plasticity after TBI.