Granulocyte colony stimulating factor reduces brain injury in a cardiopulmonary bypass-circulatory arrest model of ischemia in a newborn piglet.

Granulocyte colony stimulating factor reduces brain injury in a cardiopulmonary bypass-circulatory arrest model of ischemia in a newborn piglet.
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DOI:
10.1007/s11064-014-1399-7
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发表时间:
2014-11
影响因子:
4.4
通讯作者:
Pastuszko, Anna
Pastuszko, Anna
中科院分区:
医学3区
文献类型:
--
作者:
Pastuszko, Peter;Schears, Gregory J.;Greeley, William J.;Kubin, Joanna;Wilson, David F.;Pastuszko, Anna

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缺血性脑损伤仍然是接受先天性心脏病体外循环(CPB)手术的患者的主要关注点。纹状体和海马在这些过程中特别容易受到损伤。我们的假设是,由CPB和相关的循环停搏引起的神经元损伤至少可以部分地通过用粒细胞集落刺激因子(G-CSF)预处理来改善。将14头雄性新生仔猪分为三组:深低温停循环(DHCA)组、DHCA + G-CSF组和假手术组。将前两组置于CPB上,冷却至18°C,进行60分钟的DHCA,再温热并恢复8-9小时。实验结束后,将脑组织灌流、固定并切成10 μm的横切片。通过原位DNA片段化测定(TUNEL)观察凋亡细胞,损伤细胞的密度表示为平均数± SD/mm 2。DHCA后纹状体和海马CA 1和CA 3区的损伤细胞数量显著增加。在纹状体中,从0.46±0.37增加到3.67±1.57(p=0.002);在CA 1中,从0.11±0.19增加到5.16±1.57(p=0.001),在CA 3中,从0.28±0.25增加到2.98±1.82(p=0.040)。转流前注射G-CSF显著减少了纹状体和CA 1区的损伤细胞数量,分别减少了51%和37%。在CA 3区,G-CSF和对照组之间的损伤细胞密度没有差异。在与CPB相关的缺氧性脑损伤模型中,G-CSF显著减少了对认知功能重要的脑区域中的神经元损伤,表明它可以显著改善需要DHCA的程序的神经结局。
Ischemic brain injury continues to be of major concern in patients undergoing cardiopulmonary bypass (CPB) surgery for congenital heart disease. Striatum and hippocampus are particularly vulnerable to injury during these processes. Our hypothesis is that the neuronal injury resulting from CPB and the associated circulatory arrest can be at least partly ameliorated by pre-treatment with granulocyte colony stimulating factor (G-CSF). Fourteen male newborn piglets were assigned to three groups: deep hypothermic circulatory arrest (DHCA), DHCA with G-CSF, and sham-operated. The first two groups were placed on CPB, cooled to 18°C, subjected to 60 min of DHCA, re-warmed and recovered for 8-9 hrs. At the end of experiment, the brains were perfused, fixed and cut into 10 μm transverse sections. Apoptotic cells were visualized by in-situ DNA fragmentation assay (TUNEL), with the density of injured cells expressed as a mean number ± SD per mm2. The number of injured cells in the striatum and CA1 and CA3 regions of the hippocampus increased significantly following DHCA. In the striatum, the increase was from 0.46±0.37 to 3.67±1.57 (p=0.002); in the CA1, from 0.11±0.19 to 5.16±1.57 (p=0.001), and in the CA3, from 0.28±0.25 to 2.98±1.82 (p=0.040). Injection of G-CSF prior to bypass significantly reduced the number of injured cells in the striatum and CA1 region, by 51% and 37%, respectively. In the CA3 region, injured cell density did not differ between the G-CSF and control group. In a model of hypoxic brain insult associated with CPB, G-CSF significantly reduces neuronal injury in brain regions important for cognitive functions, suggesting it can significantly improve neurological outcomes from procedures requiring DHCA.
DOI: 10.1182/blood.v95.5.1656.005k29_1656_1662
发表时间: 2000-03-01
期刊: BLOOD
影响因子: 20.3
作者:
Dong, F;Larner, AC
通讯作者: Larner, AC
DOI: 10.1161/01.cir.0000032915.33237.72
发表时间: 2002-09-24
期刊: CIRCULATION
影响因子: 37.8
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发表时间: 2010-12-01
影响因子: 6
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DOI: 10.1111/j.1471-4159.2006.03727.x
发表时间: 2006-05-01
影响因子: 4.7
作者:
Meuer, K;Pitzer, C;Weishaupt, JH
通讯作者: Weishaupt, JH