Beneficial Effect of Erythropoietin on Sensorimotor Function and White Matter After Hypoxia-Ischemia in Neonatal Mice
Beneficial Effect of Erythropoietin on Sensorimotor Function and White Matter After Hypoxia-Ischemia in Neonatal Mice
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DOI：
10.1203/pdr.0b013e3181fcbef3
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发表时间：
2011-01-01
影响因子：
3.6
通讯作者：
van Bel, Frank
中科院分区：
文献类型：
--
作者：
Fan, Xiyong;Heijnen, Cob J.;van Bel, Frank
关于促红细胞生成素（EPO）在出生窒息动物模型中的神经保护作用，有不同的报道。我们研究了EPO对小鼠新生儿缺氧缺血性脑损伤后短期和长期预后的影响，并比较了两种不同剂量的EPO方案的影响。将9日龄小鼠置于HI后，分别于HI后0、24和48 h以5或20 kU/kg的剂量ig注射EPO。用圆柱体饲养试验（CRT）中的爪偏好作为感觉运动功能的测量指标。仅在雌性小鼠中，注射5ku /kg而不是20ku /kg的EPO可改善感觉运动功能，减少纹状体萎缩和海马病变体积，并在HI后4周和9周增强髓鞘碱性蛋白（MBP）染色。此外，在HI后72 h， EPO 5 kU/kg处理后，在室下区和齿状回发现更多的Ki67细胞，表明祖细胞增殖增加。综上所述，EPO可改善新生儿HI后的感觉运动功能，防止纹状体萎缩、海马损伤和白质丢失。促生成素的保护作用是剂量依赖性的，而且只存在于女性中。（儿科研究69:56-61,2011）
There are mixed reports on the neuroprotective properties of erythropoietin (EPO) in animal models of birth asphyxia. We investigated the effect of EPO on short- and long-term outcome after neonatal hypoxic-ischemic (HI) brain injury in mice and compared the effect of two different dose regimens of EPO. Nine-day-old mice were subjected to HI, and EPO was injected i.p. at 0, 24, and 48 h after HI in a dose of either 5 or 20 kU/kg. Paw preference in the cylinder rearing test (CRT) was used as a measure of sensorimotor function. Only in female mice, administration of EPO at 5 kU/kg but not 20 kU/kg improved sensorimotor function, reduced striatum atrophy and hippocampal lesion volume, and enhanced myelin basic protein (MBP) staining as determined at 4 and 9 wk after HI. In addition, at 72 h after HI, more Ki67 cells were found in the subventricular zone and dentate gyrus after EPO 5 kU/kg treatment, indicating an increase in progenitor cell proliferation. In conclusion, EPO improves sensorimotor function after neonatal HI and protects against striatum atrophy, hippocampus injury, and white matter loss. The protective effect of EPO is dose-dependent and only present in females. (Pediatr Res 69: 56-61, 2011)