Limits...
Oral antioxidant therapy for juvenile rats with kaolin-induced hydrocephalus.

Di Curzio DL, Turner-Brannen E, Del Bigio MR - Fluids Barriers CNS (2014)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusion: The antioxidant cocktail showed no therapeutic benefits for juvenile rats with kaolin-induced hydrocephalus although canola oil might have mild benefit.

No MeSH data available.


Related in: MedlinePlus

Bar graph showing the lateral ventricles to frontal cerebrum brain area ratios (%) from the MR images for the nonhydrocephalic control rats compared to the four hydrocephalic treatment groups before and after antioxidant therapy. All hydrocephalic groups had significantly enlarged ventricles compared to the nonhydrocephalic rats before and after treatment. * - Indicates significant increases in lateral ventricles to brain area ratios after treatment compared to before at p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4199774&req=5

Figure 2: Bar graph showing the lateral ventricles to frontal cerebrum brain area ratios (%) from the MR images for the nonhydrocephalic control rats compared to the four hydrocephalic treatment groups before and after antioxidant therapy. All hydrocephalic groups had significantly enlarged ventricles compared to the nonhydrocephalic rats before and after treatment. * - Indicates significant increases in lateral ventricles to brain area ratios after treatment compared to before at p < 0.05.

Mentions: The first MR images showed that kaolin injections into the cisterna magna lead to dilatation of the cerebral ventricles in five-week old rats (Figure 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 p < 0.05, t-tests; Tables 1 and 2; Figure 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 (p = 0.012 and 0.041, respectively), but there was no benefit above canola oil vehicle-treated hydrocephalic rats (Table 2).


Oral antioxidant therapy for juvenile rats with kaolin-induced hydrocephalus.

Di Curzio DL, Turner-Brannen E, Del Bigio MR - Fluids Barriers CNS (2014)

Bar graph showing the lateral ventricles to frontal cerebrum brain area ratios (%) from the MR images for the nonhydrocephalic control rats compared to the four hydrocephalic treatment groups before and after antioxidant therapy. All hydrocephalic groups had significantly enlarged ventricles compared to the nonhydrocephalic rats before and after treatment. * - Indicates significant increases in lateral ventricles to brain area ratios after treatment compared to before at p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4199774&req=5

Figure 2: Bar graph showing the lateral ventricles to frontal cerebrum brain area ratios (%) from the MR images for the nonhydrocephalic control rats compared to the four hydrocephalic treatment groups before and after antioxidant therapy. All hydrocephalic groups had significantly enlarged ventricles compared to the nonhydrocephalic rats before and after treatment. * - Indicates significant increases in lateral ventricles to brain area ratios after treatment compared to before at p < 0.05.
Mentions: The first MR images showed that kaolin injections into the cisterna magna lead to dilatation of the cerebral ventricles in five-week old rats (Figure 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 p < 0.05, t-tests; Tables 1 and 2; Figure 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 (p = 0.012 and 0.041, respectively), but there was no benefit above canola oil vehicle-treated hydrocephalic rats (Table 2).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusion: The antioxidant cocktail showed no therapeutic benefits for juvenile rats with kaolin-induced hydrocephalus although canola oil might have mild benefit.

No MeSH data available.


Related in: MedlinePlus