Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy.

Abstract

Thiamine (vitamin B1) deficiency, associated with a variety of conditions, including chronic alcoholism and bariatric surgery for morbid obesity, can result in the neurological disorder Wernicke's encephalopathy (WE). Recent work building upon early observations in animal models of thiamine deficiency has demonstrated an inflammatory component to the neuropathology observed in thiamine deficiency. The present, multilevel study including in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) and postmortem quantification of chemokine and cytokine proteins sought to determine whether a combination of these in vivo neuroimaging tools could be used to characterize an in vivo MR signature for neuroinflammation. Thiamine deficiency for 12days was used to model neuroinflammation; glucose loading in thiamine deficiency was used to accelerate neurodegeneration. Among 38 animals with regional brain tissue assayed postmortem for cytokine/chemokine protein levels, three groups of rats (controls+glucose, n=6; pyrithiamine+saline, n=5; pyrithiamine+glucose, n=13) underwent MRI/MRS at baseline (time 1), after 12days of treatment (time 2), and 3h after challenge (glucose or saline, time 3). In the thalamus of glucose-challenged, thiamine deficient animals, correlations between in vivo measures of pathology (lower levels of N-acetyle aspartate and higher levels of lactate) and postmortem levels of monocyte chemotactic protein-1 (MCP-1, also known as chemokine ligand 2, CCL2) support a role for this chemokine in thiamine deficiency-related neurodegeneration, but do not provide a unique in vivo signature for neuroinflammation.

• Authors: Natalie M Zahr, Carsten Alt, Dirk Mayer, Torsten Rohlfing, Amy Manning-Bog, Richard Luong, Edith V Sullivan, Adolf Pfefferbaum
• Journal: Experimental neurology (Exp Neurol) Vol. 261 Pg. 109-19 (Nov 2014) ISSN: 1090-2430 [Electronic] United States
• PMID: 24973622 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Aspartic Acid
• N-acetylaspartate
• Creatine
• Thiamine

Topics

• Analysis of Variance
• Animals
• Aspartic Acid (analogs & derivatives, metabolism)
• Brain (metabolism)
• Creatine (metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Liver (pathology)
• Magnetic Resonance Imaging
• Magnetic Resonance Spectroscopy
• Male
• Neurologic Examination
• Rats
• Rats, Wistar
• Thiamine (metabolism)
• Time Factors
• Wernicke Encephalopathy (metabolism, pathology)