Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

Pfefferbaum, Adolf; Adalsteinsson, Elfar; Bell, Richard L.; Sullivan, Edith V.

doi:10.1038/sj.npp.1301107

Cited by 46 publications

(48 citation statements)

References 113 publications

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“…Fewer in vivo studies have been conducted in animal models of alcoholism, but those, too, indicate the sensitivity of NAA to the detection of tissue compromise induced by alcohol plus nutritional deficiency (Pfefferbaum, et al, 2006). In addition to NAA, Glu is of particular interest in studies of alcoholism .…”

Section: Introductionmentioning

confidence: 99%

“…In vivo magnetic resonance spectroscopy (MRS) permits non-invasive longitudinal tracking of brain chemistry changes that can accompany aging, neurodegenerative disease, drug addiction and experimental manipulations in animals modeling such conditions (Adalsteinsson, et al, 2006;De Stefano, et al, 1998;Filippi, et al, 1999;Pfefferbaum, et al, 2006). While MRS has proven invaluable as an in vivo assessment tool, there have been technical limitations to overcome.…”

Section: Introductionmentioning

confidence: 99%

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In vivo metabolite differences between the basal ganglia and cerebellum of the rat brain detected with proton MRS at 3T

Mayer

Zahr

Sullivan

et al. 2007

Psychiatry Research: Neuroimaging

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In vivo magnetic resonance spectroscopy (MRS) enables non-invasive longitudinal tracking of brain chemistry changes that can accompany aging, neurodegenerative disease, drug addiction and experimental manipulations in animals modeling such conditions. J-coupled resonances, such as glutamate, which are highly relevant to neuropsychiatric conditions are difficult to resolve on a clinical 3T MR scanner using conventional one-dimensional MRS sequences. We, therefore, implemented Constant Time PRESS (CT-PRESS) to quantify major metabolite and neurotransmitter biochemical signals, including glutamate, in two brain regions of the rat-basal ganglia and cerebellum. We acquired spectra at two distinct time points in two independent groups of six rats and analyzed metabolite levels using either creatine or water as a reference. Our results provide evidence that CT-PRESS at 3T is adequate and reliable for in vivo detection and quantification of glutamate in the rat brain and that regional differences occur in the signal intensities of the major metabolites. That the directionality of the differences depends on whether creatine or water is used as a reference for metabolite levels emphasizes the benefit to in vivo MRS of incorporating methods to establish absolute baseline metabolite concentrations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivo metabolite differences between the basal ganglia and cerebellum of the rat brain detected with proton MRS at 3T

Mayer

Zahr

Sullivan

et al. 2007

Psychiatry Research: Neuroimaging

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“…In vivo these rats showed significant changes in the early stages of pyrithiamine treatment followed by partial recovery with thiamine repletion. The pyrithiamine rats with prior alcohol exposure exhibited attenuated recovery in the thalamus in terms of structure and a marker of neuronal viability, N-acetylaspartate, and arrested growth of the corpus callosum, compared with other rats (Pfefferbaum et al, 2006a). In a similar postmortem study in rats using the pyrithiamine model (but not MRI or MRS), severe thiamine deficiency resulted in shrinkage of the corpus callosum (Langlais and Zhang, 1997).…”

Section: Discussionmentioning

confidence: 89%

“…At the end of the thiamine deprivation period, regular thiamine-enriched chow was resumed for all animals (vitamin and mineral enriched Teklad mouse and rat diet #7001; Madison, WI), and 2 weeks later the 10 pyrithiamine-treated animals were administered 100 mg/kg thiamine i.p. The full protocol and in vivo outcome measures have been reported (Pfefferbaum et al, 2006a).…”

Section: Thiamine Deprivation Treatmentmentioning

confidence: 99%

“…The present postmortem analysis used electron microscopy in the rats previously examined longitudinally with MRI before and after (Pfefferbaum et al, 2006b) alcohol exposure and thiamine depletion and repletion (Pfefferbaum et al, 2006a). In vivo measurements of the corpus callosum indicated 36% growth over 12 months without alcohol exposure and attenuation of growth with substantial voluntary alcohol consumption and adequate nutrition, and further arrested growth with thiamine depletion.…”

Section: Introductionmentioning

confidence: 97%

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Interaction of Thiamine Deficiency and Voluntary Alcohol Consumption Disrupts Rat Corpus Callosum Ultrastructure

Sullivan

Stankovic

et al. 2007

Neuropsychopharmacol

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The relative roles of alcohol and thiamine deficiency in causing brain damage remain controversial in alcoholics without the WernickeKorsakoff syndrome. Experimental control over alcohol consumption and diet are impossible in humans but can be accomplished in animal models. This experiment was designed to differentiate the separate and combined effects on the macro-and ultrastructure of the corpus callosum of thiamine deficiency and voluntary alcohol consumption. Adult male alcohol-preferring (P) rats (9 chronically alcoholexposed and 9 water controls) received a thiamine-deficient diet for 2 weeks. There were four groups: five rats previously exposed to alcohol were treated with pyrithiamine (a thiamine phosphorylation inhibitor); five rats never exposed to alcohol were treated with pyrithiamine; four alcohol-exposed rats were treated with thiamine; and four rats never exposed to alcohol were treated with thiamine. On day 14, thiamine was restored in all 18 rats; 2 weeks later the 10 pyrithiamine-treated rats received intraperitoneal thiamine. The rats were perfused 61 days post-pyrithiamine treatment at age 598 days. Brains were dissected and weight and volumes were calculated. Sagittal sections were stained to measure white matter structures. The corpus callosum was examined using transmission electron microscopy to determine density of myelinated fibers, fiber diameter, and myelin thickness. The corpus callosum in the alcohol/ pyrithiamine group was significantly thinner, had greater fiber density, higher percentage of small fibers, and myelin thinning than in the alcohol/thiamine and water/thiamine groups. Several measures showed a graded effect, where the alcohol/pyrithiamine group had greater pathology than the water/pyrithiamine group, which had greater pathology than the two thiamine-replete groups. Across all 16 rats, thinner myelin sheaths correlated with higher percentage of small fibers. Myelin thickness and axon diameter together accounted for 71% of the variance associated with percentage of small fibers. Significant abnormalities in the alcohol/pyrithiamine group and lack of abnormality in the alcohol-exposed/thiamine-replete group indicate that thiamine deficiency caused white matter damage. The graded abnormalities across the dually to singly treated animals support a compounding effect of alcohol exposure and thiamine depletion, and indicate the potential for interaction between alcohol and thiamine deficiency in human alcohol-related brain damage.

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Neuroimaging in alcohol use disorder: From mouse to man

Fritz

Klawonn

Zahr

2019

J of Neuroscience Research

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This article provides an overview of recent advances in understanding the effects of alcohol use disorders (AUD) on the brain from the perspective of magnetic resonance imaging (MRI) research in preclinical models and clinical studies. As a noninvasive investigational tool permitting assessment of morphological, metabolic, and hemodynamic changes over time, MRI offers insight into the dynamic course of alcoholism beginning with initial exposure through periods of binge drinking and escalation, sobriety, and relapse and has been useful in differential diagnosis of neurological diseases associated with AUD. Structural MRI has revealed acute and chronic effects of alcohol on both white and gray matter volumes. MR Spectroscopy, able to quantify brain metabolites in vivo, has shed light on biochemical alterations associated with alcoholism. Diffusion tensor imaging permits microstructural characterization of white matter fiber tracts. Functional MRI has allowed for elucidation of hemodynamic responses at rest and during task engagement. Positron emission tomography, a non‐MRI imaging tool, has led to a deeper understanding of alcohol‐induced receptor and neurotransmitter changes during various stages of drinking and abstinence. Together, such in vivo imaging tools have expanded our understanding of the dynamic course of alcoholism including evidence for regional specificity of the effects of AUD, hints at mechanisms underlying the shift from casual to compulsive use of alcohol, and profound recovery with sustained abstinence.

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Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

Cited by 46 publications

References 113 publications

In vivo metabolite differences between the basal ganglia and cerebellum of the rat brain detected with proton MRS at 3T

In vivo metabolite differences between the basal ganglia and cerebellum of the rat brain detected with proton MRS at 3T

Interaction of Thiamine Deficiency and Voluntary Alcohol Consumption Disrupts Rat Corpus Callosum Ultrastructure

Neuroimaging in alcohol use disorder: From mouse to man

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