Abstract
BackgroundBoth hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old.MethodsCerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate) were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus) from both hemispheres.ResultsIn the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage.ConclusionsWe conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.
Highlights
Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia
Basal brain levels of metabolites in young and aged rats In the control untreated age-groups, i.e., young and aged normoxic rats, as opposed to the experimentally treated groups outlined in the paragraphs below, statistical analysis revealed no significant difference between the two brain hemispheres; the concentration of each metabolite was averaged from the pooled data representing the symmetric brain areas in each rat
We set out to investigate the age-differences in the content of brain metabolites in response to varying oxygen supply on the background of ischemic insult. To this end we developed a model of cerebral ischemia associated with exposure to chronic hypoxia and hyperoxia in two contrasting agegroups of rats, young and senescent, in which selected metabolites were quantified by means of proton magnetic resonance spectroscopy
Summary
Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. It is well established that mitochondrial dysfunction and oxidative damage are essential in the slowly progressive neuronal death that is characteristic of aging and neurodegenerative disorders, including Alzheimer and Parkinson's diseases [1,2,3]. Antioxidant defense systems can be upregulated in response to increased reactive oxygen species (ROS) [1] These systems may confer protection against ROS, they are not fully effective in preventing oxidative damage. Oxidative stress is considered the prevalent mechanism by which impaired cerebral blood flow, hypoxia, and hyperoxia all cause neuronal damage at the mitochondrial level due to increased ROS production that overwhelms the antioxidant capacity [6,7,8]. Evidence accumulates that reduced cerebral blood flow plays a role in the pathogenesis of Alzheimer's disease [9] and contributes to cognitive decline which is usually present during aging [10]
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