The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats
The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats
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DOI：
10.1016/j.brainres.2006.12.023
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发表时间：
2007-03-09
期刊：
影响因子：
2.9
通讯作者：
Zhang, John H.
中科院分区：
文献类型：
--
作者：
Matchett, Gerald A.;Calinisan, Jason B.;Zhang, John H.
粒细胞集落刺激因子(G-CSF)是一种造血系统内源性多肽类激素，目前已进入I/II期临床试验。严重的术中低血压可导致全脑缺血和海马区神经元的凋亡丢失。我们在大鼠全脑缺血模型上测试了G-CSF。雄性SD大鼠(280~330g)采用双血管阻断模型(出血性低血压至平均动脉压30~35 mm Hg，双侧颈总动脉阻断8min)复制全脑缺血模型。动物分为三组：未治疗组(GI，n=49)、G-CSF治疗组(GI+G-CSF，n=42)和假手术组(Sham，n=26)。治疗组术前12h、手术当天、术后第1天皮下注射G-CSF(50 mg/kg)，分别于术后第2、3、14天处死大鼠。T迷宫自发交替测试显示，G-CSF治疗组有初步改善，但没有长期益处。每日体重测量显示，G-CSF组有改善的初步趋势。海马尼氏定量组织学在第3天和第14天显示出相同的结果，这一结果得到了定量TUNEL染色的支持。免疫组织化学和Western印迹显示，GI+G-CSF组在第2天开始出现磷酸化AKT的增加。我们得出结论，G-CSF治疗与全脑缺血合并轻度高血糖后神经行为结果的短暂早期改善有关，但没有长期保护作用。(C)2006爱思唯尔B.V.保留所有权利。
Granulocyte-colony stimulating factor (G-CSF) is an endogenous peptide hormone of the hematopoietic system that has entered Phase I/II clinical trials for treatment of ischemic stroke. Severe intraoperative hypotension can lead to global cerebral ischemia and apoptotic neuron loss within the hippocampus. We tested G-CSF in a rat model of global cerebral ischemia. Global cerebral ischernia was induced in male Sprague-Dawley rats (280-330 g) with the 2-vessel occlusion model (hemorrhagic hypotension to a mean arterial pressure of 30-35 mm Hg and bilateral common carotid artery occlusion for 8 min). Three groups of animals were used: global ischernia without treatment (GI, n = 49), global ischernia with G-CSF treatment (GI+G-CSF, n=42), and sham surgery (Sham, n=26). Rats in the treatment group received G-CSF (50 mu g/kg, subcutaneously) 12 h before surgery, on the day of surgery, and on postoperative Day I and were euthanized on Days 2, 3, and 14. Mild hyperglycemia was observed in all groups. T-maze testing for spontaneous alternation demonstrated initial improvement in the G-CSF treatment group but no long-term benefit. Measurement of daily body weight demonstrated an initial trend toward improvement in the G-CSF group. Quantitative Nissl histology of the hippocampus demonstrated equivalent outcomes on Days 3 and 14, which was supported by quantitative TUNEL stain. Immunohistochemistry and Western blot demonstrated an initial increase in phosphorylated-AKT in the GI + G-CSF group on Day 2. We conclude that G-CSF treatment is associated with transient early improvement in neurobehavioral outcomes after global ischemia complicated by mild hyperglycemia, but no long-term protection. (c) 2006 Elsevier B.V. All rights reserved.