Departments of Human Anatomy & Cell Science, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada ; Manitoba Institute of Child Health, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada.
Manitoba Institute of Child Health, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada.
Fluids Barriers CNS. 2014 Oct 13;11:23. doi: 10.1186/2045-8118-11-23. eCollection 2014.
Oxidative and nitrosylative changes have been shown to occur in conjunction with the hypoxic changes and cellular/axonal damage in hydrocephalic rodent brains. We hypothesized that antioxidant therapy would improve behavioral, neurophysiological, and/or neurobiochemical outcomes in juvenile rats following induction of hydrocephalus.
Three-week old rats received an injection of kaolin (aluminum silicate) into the cisterna magna. Magnetic resonance (MR) imaging was performed two weeks later to assess ventricle size and stratify rats to four treatment conditions. Rats were treated for two weeks daily with sham therapy of either oral canola oil or dextrose or experimental therapy of a low or high dose of an antioxidant mixture containing α-tocopherol, L-ascorbic acid, coenzyme Q10 (CoQ10), reduced glutathione, and reduced lipoic acid. Behavior was examined thrice weekly.
All hydrocephalic groups lagged in weight gain in comparison to non-hydrocephalic controls, all developed significant ventriculomegaly, and all exhibited white matter destruction. Canola oil with or without the antioxidant mixture normalized antioxidant capacity in brain tissue, and the dextrose-treated rats had the greatest ventricular enlargement during the treatment period. However, there were no significant differences between the four treatment groups of hydrocephalic rats for the various behavioral tasks. Glial fibrillary acidic protein and myelin basic protein quantitation showed no differences between the treatment groups or with control rats. There was increased lipid peroxidation in the hydrocephalic rats compared to controls but no differences between treatment groups.
The antioxidant cocktail showed no therapeutic benefits for juvenile rats with kaolin-induced hydrocephalus although canola oil might have mild benefit.
氧化和亚硝酰基变化与低氧变化以及脑积水啮齿动物大脑中的细胞/轴突损伤同时发生。我们假设抗氧化治疗会改善脑积水诱导后幼鼠的行为、神经生理和/或神经生化结果。
三周大的大鼠接受脑室内硅酸铝（高岭土）注射。两周后进行磁共振（MR）成像以评估脑室大小，并将大鼠分层为四种治疗条件。大鼠每天接受假治疗，即口服菜籽油或葡萄糖，或实验治疗低剂量或高剂量含有α-生育酚、L-抗坏血酸、辅酶 Q10（CoQ10）、还原型谷胱甘肽和还原型硫辛酸的抗氧化混合物，持续两周。每周检查三次行为。
所有脑积水组与非脑积水对照组相比体重增长均滞后，所有组均出现明显的脑室扩大，且均表现出白质破坏。菜籽油加或不加抗氧化混合物均可使脑组织中的抗氧化能力正常化，而在治疗期间，葡萄糖处理的大鼠的脑室扩大最大。然而，脑积水大鼠的四种治疗组在各种行为任务中均无显著差异。胶质纤维酸性蛋白和髓鞘碱性蛋白定量显示，治疗组与对照组之间无差异。与对照组相比，脑积水大鼠的脂质过氧化增加，但治疗组之间无差异。
尽管菜籽油可能有轻微益处，但抗氧化鸡尾酒对高岭土诱导的脑积水幼鼠没有治疗益处。
