Stem cell transplantation is a promising intervention for neonatal hypoxic-ischemic encephalopathy (HIE); however, universal feasibility and safety have not been thoroughly evaluated. AMD3100 and insulin-like growth factor 1 (IGF1) mobilize progenitor cells into peripheral circulation. The objective of this study was to assess the short-term efficacy of inducing endogenous stem cell mobilization after injury in a model of neonatal HIE. Postnatal day 9 CD1 pups received sham surgery or unilateral carotid artery ligation and 30 min of hypoxia followed by saline, AMD3100, IGF1, or both agents. Intraperitoneal injections of 5-ethynyl-2′-deoxy­uridine (EdU) and 5-bromo-2′-deoxyuridine were used to ­label replicating progenitor cells. At P14, animals underwent rotarod testing, and the brains were sectioned for area measurements and immunofluorescence staining. Comparisons were made using one-way analysis of variance. Spearman’s rho was calculated to assess correlation between rotarod results and markers of brain injury. Pups treated with both agents had improved rotarod performance (p = 0.02) and increased EdU+ progenitor cells in the subgranular zone (SGZ) compared to injured controls (p = 0.10). An increase in active cells within the SGZ was correlated with improved rotarod performance (r = 0.84, p = 0.04). There were no differences in overall injury score or in brain area or number of activated cells in the subventricular zone between the treatment groups. Combined treatment with AMD3100 and IGF1 shows promise for decreasing brain injury and improving motor function in pups after HIE which correlated with changes in the number of active progenitor cells in the SGZ.
Dev Neurosci

中文翻译：

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胰岛素样生长因子1和AMD3100的联合治疗可改善新生儿缺氧缺血性脑病的小鼠模型的运动结果。

干细胞移植是新生儿缺氧缺血性脑病（HIE）的一种有前途的干预措施。但是，普遍可行性和安全性尚未得到彻底评估。AMD3100和胰岛素样生长因子1（IGF1）动员祖细胞进入外周循环。这项研究的目的是评估在新生儿HIE模型中，在损伤后诱导内源性干细胞动员的短期疗效。出生后第9天的CD1幼犬接受了假手术或单侧颈动脉结扎和缺氧30分钟，然后接受生理盐水，AMD3100，IGF1或两种药物治疗。腹腔注射5-乙炔基-2'-脱氧尿苷（EdU）和5-溴-2'-脱氧尿苷用于标记复制祖细胞。在P14时，动物接受了旋转脚架测试，然后将大脑切成薄片进行面积测量和免疫荧光染色。使用单向方差分析进行比较。计算Spearman的rho来评估轮状试验结果与脑损伤标志物之间的相关性。两种药剂处理的幼仔都有改善的轮尺性能（p = 0.02），并且与受伤的对照组相比，亚颗粒区（SGZ）中的EdU +祖细胞增加（p = 0.10）。SGZ内活动细胞的增加与旋转杆性能的提高相关（r = 0.84，p = 0.04）。治疗组之间的总体损伤评分或脑区域或脑室下区域的活化细胞数量没有差异。AMD3100和IGF1的联合治疗显示出有望减轻HIE后幼犬的脑损伤并改善其运动功能，这与SGZ中活性祖细胞数量的变化有关。
开发神经科学