Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

Macrì, Monica; d’Alessandro, Nicola; Giulio, Camillo Di; Iorio, Patrizia Di; Luzio, S. Di; Giuliani, Patricia; Esposito, Ennio; Pokorski, Mieczysław

doi:10.1186/1423-0127-17-14

Cited by 37 publications

(23 citation statements)

References 31 publications

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“…From another perspective, the antidepressant phenelzine, a monoamine oxidase inhibitor, also elevates rat brain levels of alanine by inhibition of aminotransferase activity [65]. It is noteworthy that ischemia–hypoxia also caused decreased alanine levels in the rat brain [66], which is in a line with our observations.…”

Section: Discussionsupporting

confidence: 86%

Neurochemical alterations in frontal cortex of the rat after one week of hypobaric hypoxia

Bogdanova

Abdullah

Kanekar

et al. 2014

Behavioural Brain Research

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Residing at high altitude may lead to reduced blood oxygen saturation in the brain and altered metabolism in frontal cortical brain areas, probably due to chronic hypobaric hypoxia. These changes may underlie the increased rates of depression and suicidal behavior that have been associated with life at higher altitudes. To test the hypothesis that hypobaric hypoxia is responsible for development of mood disorders due to alterations in neurochemistry, we assessed depression-like behavior in parallel to levels of brain metabolites in rats housed at simulated altitude. 32 female Sprague Dawley rats were housed either in a hypobaric hypoxia chamber at 10,000 ft of simulated altitude for 1 week or at local conditions (4500 ft of elevation in Salt Lake City, Utah). Depression-like behavior was assessed using the forced swim test (FST) and levels of neurometabolites were estimated by in vivo proton magnetic resonance spectroscopy in the frontal cortex, the striatum and the hippocampus at baseline and after a week of exposure to hypobaric hypoxia. After hypoxia exposure the animals demonstrated increased immobility behavior and shortened latency to immobility in the FST. Elevated ratios of myo-inositol, glutamate, and the sum of myo-inositol and glycine to total creatine were observed in the frontal cortex of hypoxia treated rats. A decrease in the ratio of alanine to total creatine was also noted. This study shows that hypoxia induced alterations in frontal lobe brain metabolites, aggravated depression-like behavior and might be a factor in increased rates of psychiatric disorders observed in populations living at high altitudes.

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Section: Discussionsupporting

confidence: 86%

Neurochemical alterations in frontal cortex of the rat after one week of hypobaric hypoxia

Bogdanova

Abdullah

Kanekar

et al. 2014

Behavioural Brain Research

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“…In the present work, the cardiorespiratory reflexes induced by carotid ischemia were similar in young and old rats. Previous work has addressed the impairment of carotid ischemia on cerebral oxidative balance caused by permanent ligation of the right carotid artery (Macri et al 2010) in old animals. These are long-term ischemia and the authors did not address the effects of the ventilatory reflexes induced by carotid ischemia in aged animals, shown for the first time in the present work.…”

Section: Discussionmentioning

confidence: 99%

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Monteiro

Batuca

Obeso

et al. 2010

AGE

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The carotid body (CB) is the main arterial chemoreceptor with a low threshold to hypoxia. CB activity is augmented by A 2 -adenosine receptors stimulation and attenuated by D 2 -dopamine receptors. The effect of aging on ventilatory responses mediated by the CB to hypoxia, ischemia, and to adenosine and dopamine administration is almost unknown. This study aims to investigate the ventilatory response to ischemia and to adenosine, dopamine, and their antagonists in old rats, as well as the effect of hypoxia on adenosine 3′,5′-cyclic monophosphate (cAMP) accumulation in the aged CB. In vivo experiments were performed on young and aged rats anesthetized with pentobarbitone and breathing spontaneously. CB ischemia was induced AGE (2011) 33:337-350 DOI 10.1007 Scientific knowledge on the subject The functional ventilatory consequences of the morphological and molecular changes in the carotid body observed in aged animals, as well as the ventilatory effects of dopamine and adenosine in old animals, are still unknown.What this study adds to the field The carotid body's peripheral control of ventilation is not impaired by aging. The preservation of the inhibitory and excitatory effects on ventilation caused by exogenous dopamine and adenosine, respectively, should be taken into account in the therapeutic use of these amines and their agonists and antagonists in elderly people. by bilateral common carotid occlusions. cAMP content was measured in CB incubated with different oxygen concentrations. Hyperoxia caused a decrease in cAMP in the CB at all ages, but no differences were found between normoxia and hypoxia or between young and old animals. The endogenous dopaminergic inhibitory tonus is slightly reduced. However, both the ventilation decrease caused by exogenous dopamine and the increase mediated by A 2A -adenosine receptors are not impaired in aged animals. The bradycardia induced by adenosine is attenuated in old rats. The CB's peripheral control of ventilation is preserved during aging. Concerns have also arisen regarding the clinical usage of adenosine to revert supraventricular tachycardia and the use of dopamine in critical care situations involving elderly people.

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“…(13, 14) Hypoxia is associated with hippocampal neuronal death in animal models. (15, 16) Despite these possible central nervous system effects of asthma, few studies, to date, have used neuroimaging to examine brain structure or functioning in asthma patients and none have focused on the hippocampus. A small study using MRI in mild to moderate asthma found that 13 out of 21 (62%) participants had incidental brain MRI abnormalities (including deep white matter hyperintensities, perivascular space, and abnormal anatomic findings).…”

Section: Introductionmentioning

confidence: 99%

Hippocampal volume in patients with asthma: Results from the Dallas Heart Study

Carlson

Kim

Khan³

et al. 2016

Journal of Asthma

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Introduction Asthma is associated with an increased risk of mild cognitive impairment and dementia. Depression and oral corticosteroid use are associated with atrophy of the hippocampus and are common in asthma. However, minimal neuroimaging data are available in asthma patients. Methods We conducted a retrospective analysis of 1,287 adult participants from the Dallas Heart Study, an epidemiological sample of Dallas County residents. Study outcome variables were hippocampal volumes measured by FreeSurfer. ANOVA was used to examine a gender difference in hippocampal volumes. General Linear Models (GLM) were conducted to examine asthma diagnosis association with hippocampal volumes. Results The prevalence rate of asthma among our study sample was 10.8% with 9.6% in males and 11.7% in females. After controlling for demographic characteristics, participants with asthma had significantly smaller total, right, and left hippocampal volumes than those without asthma. The association of asthma with smaller hippocampal volume was significant among males but not among females. Conclusion Hippocampal volume in a large and diverse sample of adults was significantly smaller in people with asthma as compared to those without asthma. These findings suggest that asthma may be associated with structural brain differences. Thus, medical illnesses without obvious direct neurodegenerative or even vascular involvement can be associated with brain changes. Because the hippocampus is a brain region involved in memory formation, these findings may have implications for treatment adherence which could have important implications for asthma treatment. Study limitations are the reliance on a self-reported asthma diagnosis and lack of additional asthma clinical information.

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Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

Cited by 37 publications

References 31 publications

Neurochemical alterations in frontal cortex of the rat after one week of hypobaric hypoxia

Neurochemical alterations in frontal cortex of the rat after one week of hypobaric hypoxia

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Hippocampal volume in patients with asthma: Results from the Dallas Heart Study

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