Background Oxidative and nitrosylative changes have been shown to occur in

Background Oxidative and nitrosylative changes have been shown to occur in conjunction with the hypoxic changes and cellular/axonal damage in hydrocephalic rodent brains. dose of an antioxidant mixture made up of -tocopherol, L-ascorbic acid, coenzyme Q10 (CoQ10), reduced glutathione, and reduced lipoic acid. Behavior was examined thrice weekly. Results All hydrocephalic purchase AZD2171 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. Conclusion The purchase AZD2171 antioxidant cocktail showed no therapeutic benefits for juvenile rats with kaolin-induced hydrocephalus although canola oil might have moderate benefit. values??0.05 were deemed statistically significant. Statistical analyses were conducted separately for the first (n?=?45) and second (n?=?52) trials of rats, which consisted of ANOVA with post-hoc analyses conducted for some steps using the Bonferroni-Dunn multiple inter-group comparisons approaches where indicated. Non-parametric score data were analyzed with MannCWhitney test or Kruskal-Wallis test for two or three groups, respectively. For the second trial, qualitative assessments for the sham control and hydrocephalic rats were analyzed separately from quantitative steps. Two-tailed Students em t /em -assessments were conducted for behavioral testing, ventricle size, histological data, biochemical, and ELISA values to compare the control and hydrocephalus groups. Statistical analyses were conducted using the SPSS 14.0 software program. Results Mortality No animals died during kaolin injection. Of the 89 rats that were given a kaolin-injection at three weeks age, 4 were euthanized approximately two weeks post-injection before the onset of therapy and 1 died 2?days before the end of treatment because of severe neurological deficits. The remaining rats underwent the two-week antioxidant therapy regime according to the stratification of treatment conditions and were sacrificed at seven weeks of age. Age-matched control rats (n?=?8) were also euthanized at seven weeks age and 24?hours post-MRI. Ventricle size on magnetic resonance imaging The first MR images showed that kaolin injections into the cisterna Rabbit polyclonal to ZNF697 magna lead to dilatation of the cerebral ventricles in five-week aged rats (Physique?1). In both trials, there was no significant difference between the groups prior to onset of antioxidant therapy. All groups showed continued enlargement of the ventricles during the therapeutic period, and all groups displayed significant increases in lateral ventricle size compared to the images before treatment began (all em p /em ? ?0.05, em t /em -tests; Tables?1 and ?and2;2; Physique?2). In the first trial, the high dose treatment groups had the most severe ventricular enlargement with a 33.5% increase after treatment (Table?1). In the second trial, the low and high dose groups showed less ventricular enlargement than dextrose control ( em p /em ?=?0.012 and 0.041, respectively), but there was no benefit above canola oil vehicle-treated hydrocephalic rats (Table?2). Open in a separate window Physique 1 Magnetic resonance (MR) images displaying progressive hydrocephalus in rats at 5 and 7?weeks of age that underwent injection of kaolin into the cisterna magna at 3?weeks. These em T2 /em -weighted images depict the coronal view of the cerebral cortex at the level of the frontal horn of the lateral ventricle where purchase AZD2171 cerebrospinal fluid (CSF) is usually white (bright) in the lateral and third ventricles and subarachnoid space (SAS). The control rat images are shown at the top, and the ventricles are very narrow. Ventricular enlargement is obvious in all hydrocephalic rats before treatment, and all treated groups displayed further dilatation after treatment. Table 1 Outcomes of antioxidant treatment on hydrocephalic rats (Trial 1)* thead valign=”best” th align=”remaining” rowspan=”1″ colspan=”1″ ? /th th align=”remaining” rowspan=”1″ colspan=”1″ Dextrose /th th align=”remaining” rowspan=”1″ colspan=”1″ Low dosage antiox.? /th th align=”remaining” rowspan=”1″ colspan=”1″ Large dosage antiox.? /th /thead Test size hr / 14 hr / 14 hr / 15 hr / Ventricle region index (pre-treat) hr / 0.130??0.010 hr / 0.128??0.008 hr.