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

• Published in: Experimental neurology Vol. 261; pp. 109 - 119
• Main Authors: Zahr, Natalie M., Alt, Carsten, Mayer, Dirk, Rohlfing, Torsten, Manning-Bog, Amy, Luong, Richard, Sullivan, Edith V., Pfefferbaum, Adolf
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2014
• Subjects: Analysis of Variance; Animals; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Brain; Brain - metabolism; Creatine - metabolism; Cytokines - metabolism; Disease Models, Animal; Immunohistochemistry; Lactate; Liver; Liver - pathology; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; MCP-1; Microglia; Neurologic Examination; Rats; Rats, Wistar; TDP; Thiamine; Thiamine - metabolism; Time Factors; Wernicke Encephalopathy - metabolism; Wernicke Encephalopathy - pathology; Magnetic resonance spectroscopy; Immunohistochemistry; TDP; Brain; MCP-1; Lactate; Magnetic resonance imaging; Liver; Thiamine; Microglia
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2014.06.015

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. •In vivo MRI and postmortem brain cytokine biomarkers were identified in a controlled model of thiamine deficiency.•In vivo markers included enlarged ventricles and hyperintensities in the inferior colliculi of thiamine-deficient rats.•Glucose administration in the context of thiamine deficiency rapidly intensified in vivo brain pathology.•MCP-1 chemokine levels in the thalamus correlated selectively with in vivo measures of pathology.