title: 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: Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd., Stanford, CA 94305, USA; Neuroscience Program, SRI International, Menlo Park, CA 94025, USA. Electronic address: nzahr@stanford.edu.
authors: Natalie M
authors: NM
authors: Zahr
authors: Immunology Program, SRI International, Menlo Park, CA 94025, USA; Palo Alto Institute for Research and Education, Palo Alto, CA 94304, USA.
authors: Carsten
authors: C
authors: Alt
authors: Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd., Stanford, CA 94305, USA; Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
authors: Dirk
authors: D
authors: Mayer
authors: Neuroscience Program, SRI International, Menlo Park, CA 94025, USA.
authors: Torsten
authors: T
authors: Rohlfing
authors: Neuroscience Program, SRI International, Menlo Park, CA 94025, USA.
authors: Amy
authors: A
authors: Manning-Bog
authors: Department of Comparative Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Edwards R321, Stanford, CA 94305, USA.
authors: Richard
authors: R
authors: Luong
authors: Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd., Stanford, CA 94305, USA.
authors: Edith V
authors: EV
authors: Sullivan
authors: Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd., Stanford, CA 94305, USA; Neuroscience Program, SRI International, Menlo Park, CA 94025, USA.
authors: Adolf
authors: A
authors: Pfefferbaum
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D008099:Liver / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009460:Neurologic Examination; D051381:Rats; D017208:Rats, Wistar; D013831:Thiamine / Q000378:metabolism; D013997:Time Factors; D014899:Wernicke Encephalopathy / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016207:Cytokines; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D013831:Thiamine
keywords: Brain; Immunohistochemistry; Lactate; Liver; MCP-1; Magnetic resonance imaging; Magnetic resonance spectroscopy; Microglia; TDP; Thiamine