Erythropoietin Sustains Cognitive Function and Brain Volume after Neonatal Stroke

Erythropoietin Sustains Cognitive Function and Brain Volume after Neonatal Stroke
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DOI:
10.1159/000232558
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发表时间:
2009-01-01
影响因子:
2.9
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:
Gonzalez, Fernando F.;Abel, Regina;Ferriero, Donna M.

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新生儿中风导致死亡和严重的发病率,但目前没有有效的治疗方法。促红细胞生成素(EPO)促进脑损伤后短期内的细胞保护和神经发生;然而,长期认知结果和最佳剂量方案尚未阐明。我们在出生后第10天的大鼠中进行大脑中动脉闭塞,其用单剂量EPO(5 U/g,i. p.)再灌注后即刻,或在损伤后0小时、24小时和7天3个剂量的EPO(各lU/g,i. p.)。在损伤后3个月,用3个剂量的EPO治疗的大鼠在Morris水迷宫中与假手术没有差异,并且通常比用单剂量治疗的大鼠或溶剂治疗的损伤大鼠表现更好。这些多次给药大鼠的半球体积及其亚区域也有所增加。这些结果表明,新生儿脑损伤后,细胞修复、增殖和长期整合到神经网络中可能需要额外的、较晚剂量的EPO。版权所有(C)2009 S. Karger AG,巴塞尔
Neonatal stroke leads to mortality and severe morbidity, but there currently is no effective treatment. Erythropoietin (EPO) promotes cytoprotection and neurogenesis in the short term following brain injury; however, long-term cognitive outcomes and optimal dosing regimens have not been clarified. We performed middle cerebral artery occlusion in postnatal day 10 rats, which were treated with either a single dose of EPO (5 U/g, i.p.) immediately upon reperfusion, or 3 doses of EPO (1 U/g, i.p. each) at 0 h, 24 h, and 7 days after injury. At 3 months after injury, rats treated with 3 doses of EPO did not differ from shams in the Morris water maze, and generally performed better than either rats treated with a single dose or vehicle-treated injured rats. These multiple-dose-treated rats also had increases in hemispheric volume and its subregions. These results suggest that additional, later doses of EPO may be required for cell repair, proliferation, and long-term incorporation into neural networks after neonatal brain injury. Copyright (C) 2009 S. Karger AG, Basel