Systemic glycerol decreases neonatal rabbit brain and cerebellar growth independent of intraventricular hemorrhage.
Systemic glycerol decreases neonatal rabbit brain and cerebellar growth independent of intraventricular hemorrhage.
复制标题
全身性甘油会降低新生兔大脑和小脑的生长，与脑室内出血无关。
DOI：
10.1038/pr.2013.236
复制
发表时间：
2014
影响因子：
3.6
通讯作者：
Juul,SandraE
中科院分区：
文献类型：
--
作者：
Traudt,ChristopherM;McPherson,RonJ;Studholme,Colin;Millen,KathleenJ;Juul,SandraE
背景：小脑发育不全是早产儿和患有脑室内出血（IVH）的婴儿的常见问题。方法：新西兰白色大白兔2d早产，腹腔注射甘油（3.25- 6.5g/kg），观察IVH对小脑生长发育的影响。对照组在足月时出生。超声检查证实IVH。在2周的生命中，通过磁共振成像、小脑叶状结构、增殖（Ki-67）和浦肯野细胞密度测定脑体积。组织甘油和谷胱甘肽浓度measured.Results：甘油增加IVH，蛛网膜下腔出血，死亡率呈剂量依赖性。小脑总体积、小脑小叶和小脑增殖以剂量依赖性方式减少。甘油在血液、脑和肝脏中迅速蓄积，并与谷胱甘肽浓度升高相关。所有这些结果是独立的IVH status.Conclusion：小脑发育不全后，甘油给药以剂量依赖性的方式诱导。鉴于甘油的快速组织蓄积、脑生长的剂量依赖性降低以及IVH对测量结果的影响缺乏，我们质疑该模型的有效性，因为不能排除甘油毒性。需要一种更好的IVH生理模型。
Background:Cerebellar hypoplasia is a common problem in preterm infants and infants suffering from intraventricular hemorrhage (IVH). To evaluate the effects of IVH on cerebellar growth and development, we used a neonatal rabbit model of systemic glycerol to produce IVH.Methods:New Zealand White rabbit kits were surgically delivered 2 d preterm and treated with intraperitoneal glycerol (3.25–6.5 g/kg). Controls were born at term. IVH was documented by ultrasonography. Brain volumes determined by magnetic resonance imaging, cerebellar foliation, proliferation (Ki-67), and Purkinje cell density were assessed at 2 wk of life. Tissue glycerol and glutathione concentrations were measured.Results:Glycerol increased IVH, subarachnoid hemorrhages, and mortality in a dose-dependent manner. Total cerebellar volumes, cerebellar foliation, and cerebellar proliferation were decreased in a dose-dependent manner. Glycerol accumulated rapidly in blood, brain, and liver and was associated with increased glutathione concentration. All of these results were independent of IVH status.Conclusion:Cerebellar hypoplasia was induced after glycerol administration in a dose-dependent manner. Given the rapid tissue accumulation of glycerol, dose-dependent decrease in brain growth, and lack of IVH effect on measured outcomes, we question the validity of this model because glycerol toxicity cannot be ruled out. A better physiological model of IVH is needed.