Delayed neuroprotective effect of insulin-like growth factor-I after experimental transient focal cerebral ischemia monitored with MRI
Delayed neuroprotective effect of insulin-like growth factor-I after experimental transient focal cerebral ischemia monitored with MRI
复制标题
DOI：
10.1161/01.str.32.5.1226
复制
发表时间：
2001-05-01
期刊：
影响因子：
8.3
通讯作者：
Schwab, S
中科院分区：
文献类型：
--
作者：
Sch채bitz, WR;Hoffmann, TT;Schwab, S
背景和目的-胰岛素样生长因子（IGF）治疗已被证明具有营养和神经保护作用，在体外和体内不同的病变模型。IGF-I在缺氧缺血性损伤和全脑缺血后具有强有力的神经保护作用。IGF-I在局灶性脑缺血中的作用仅部分了解。因此，在本研究中，我们评估，通过应用MRI监测，是否有临床意义的全身管理IGF-I可以实现一个长期持久的neuroprotective effects. Methods-雄性Wistar大鼠进行短暂闭塞的右大脑中动脉1小时，通过使用缝合闭塞模型。然后对动物进行33.33 μ g IGF-I/d心室内治疗3天（A组，IGF-I组[n=13]; B组，安慰剂组[n=14]）或皮下注射200 μ g IGF-I/d治疗7天（D组，IGF-I组[n=10]; E组，安慰剂组[n=10]）。C组和F组作为假手术对照组（分别为n=5和n=3）。在大脑中动脉闭塞后30分钟开始治疗。在血管闭塞后60分钟开始，在缺血后6小时和第1、2、5和7天，对经皮下注射治疗的动物进行MRI研究（扩散加权成像、灌注成像和T2加权成像）。每天对动物称重并进行神经学评估（评级范围从0（表示无缺陷）至5（表示死亡））。在第三天（脑室内试验）和第七天（皮下试验），动物被安乐死，脑切片用氯化三苯基四氮唑染色。结果-脑室内治疗组动物的平均梗死体积为52.9 ± 25.2 mm（3），对照组动物为146.4 ± 62.2 mm（3）（P
Background and Purpose-Insulin-like growth factor (IGF) treatment has been shown to have trophic and neuroprotective effects in vitro and in vivo in different lesion models. IGF-I has potent neuroprotective effects after hypoxic-ischemic injury and global ischemia. The role of IGF-I in focal cerebral ischemia is only partially understood. Therefore, in the present study, we evaluated, by applying MRI monitoring, whether a clinically relevant systemic administration of IGF-I can achieve a long-lasting neuroprotective effect.Methods-Male Wistar rats underwent transient occlusion of the right middle cerebral artery for 1 hour by using the suture occlusion model. Animals then were intraventricularly treated with 33.33 mug IGF-I/d for 3 days (group A, the IGF-I group [n=13]; group B, the placebo group [n=14]) or subcutaneously treated with 200 mug IGF-I/d for 7 days (group D, the IGF-I group [n=10]; group E, the placebo group [n=10]). Groups C and F served as sham-operated controls (n=5 and n=3, respectively). Treatment was begun 30 minutes after occlusion of the middle cerebral artery. Subcutaneously treated animals underwent MRI studies (diffusion-weighted imaging, perfusion imaging, and T2-weighted imaging) beginning 60 minutes after vessel occlusion at 6 hours and at days 1, 2, 5, and 7 after ischemia. The animals were weighed and neurologically assessed daily (rating scale ranged fi om 0, indicating no deficit, to 5, indicating death). On the third day (intraventricular trial) and on the seventh day (subcutaneous trial), animals were euthanized, and brain sections were stained with triphenyltetrazolium chloride.Results-The mean infarct volume was 52.9 +/- 25.2 mm(3) in intraventricularly treated animals versus 146.4 +/- 62.2 mm(3) in control animals (P