Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo
- 403 Downloads
Serious neurological concomitants of alcoholism include Wernicke’s encephalopathy (WE), Korsakoff’s syndrome (KS), and hepatic encephalopathy (HE).
This study was conducted in animal models to determine neuroradiological signatures associated with liver damage caused by carbon tetrachloride (CCl4), thiamine deficiency caused by pyrithiamine treatment, and nonspecific nutritional deficiency caused by food deprivation.
Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were used to evaluate brains of wild-type Wistar rats at baseline and following treatment.
Similar to observations in ethanol (EtOH) exposure models, thiamine deficiency caused enlargement of the lateral ventricles. Liver damage was not associated with effects on cerebrospinal fluid volumes, whereas food deprivation caused modest enlargement of the cisterns. In contrast to what has repeatedly been shown in EtOH exposure models, in which levels of choline-containing compounds (Cho) measured by MRS are elevated, Cho levels in treated animals in all three experiments (i.e., liver damage, thiamine deficiency, and food deprivation) were lower than those in baseline or controls.
These results add to the growing body of literature suggesting that MRS-detectable Cho is labile and can depend on a number of variables that are not often considered in human experiments. These results also suggest that reductions in Cho observed in humans with alcohol use disorder (AUD) may well be due to mild manifestations of concomitants of AUD such as liver damage or nutritional deficiencies and not necessarily to alcohol consumption per se.
KeywordsPyrithiamine Carbon tetrachloride Hematology Magnetic resonance Spectroscopy
This study was supported with grant funding from the NIAAA including AA005965, AA013521, and AA017168. The authors would like to acknowledge Priya Asok, Crystal Caldwell, Cheshire Hardcastle, and Matthew Serventi for their help in the data collection.
Compliance with ethical standards
The Institutional Animal Care and Use Committees (IACUC) at SRI International and Stanford University approved all research protocols in accordance with the guidelines of the IACUC of the National Institute on Drug Abuse, National Institutes of Health, and the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council 1996).
Conflict of interest
The authors declare that they have no competing interest.
- Bendszus M, Weijers HG, Wiesbeck G, Warmuth-Metz M, Bartsch AJ, Engels S, Boning J, Solymosi L (2001) Sequential MR imaging and proton MR spectroscopy in patients who underwent recent detoxification for chronic alcoholism: correlation with clinical and neuropsychological data. Am J Neuroradiol 22:1926–1932PubMedGoogle Scholar
- Cordoba J, Alonso J, Rovira A, Jacas C, Sanpedro F, Castells L, Vargas V, Margarit C, Kulisewsky J, Esteban R, Guardia J (2001) The development of low-grade cerebral edema in cirrhosis is supported by the evolution of (1)H-magnetic resonance abnormalities after liver transplantation. J Hepatol 35:598–604CrossRefPubMedGoogle Scholar
- Durazzo TC, Pathak V, Gazdzinski S, Mon A, Meyerhoff DJ (2010) Metabolite levels in the brain reward pathway discriminate those who remain abstinent from those who resume hazardous alcohol consumption after treatment for alcohol dependence. J Stud Alcohol Drugs 71:278–289CrossRefPubMedPubMedCentralGoogle Scholar
- Fein G, Meyerhoff D, Di Sclafani V, Ezekiel F, Poole N, MacKay S, Dillon WP, Constans J-M, Weiner MW (1994) 1H magnetic resonance spectroscopic imaging separates neuronal from glial changes in alcohol-related brain atrophy. In: Lancaster F (ed) Alcohol and glial cells, NIAAA Research Monograph # 27. US Government Printing Office, Bethesda, pp 227–241Google Scholar
- Hazell AS, Butterworth RF (2009) Update of cell damage mechanisms in thiamine deficiency: focus on oxidative stress, excitotoxicity and inflammationGoogle Scholar
- Kumar V, Abbas A, Fausto N, Robbins SL, Cotran RS (2005) Robbins and Cotran pathological basis of disease, 7th edn. Elsevier Saunders, Philadelphia, pp 25–26Google Scholar
- Murata T, Omata N, Fujibayashi Y, Waki A, Sadato N, Yoshimoto M, Omori M, Isaki K, Yonekura Y (1999) Dynamic changes in glucose metabolism induced by thiamine deficiency and its replenishment as revealed by a positron autoradiography technique using rat living brain slices. J Neurol Sci 164:29–36CrossRefPubMedGoogle Scholar
- Pfefferbaum A, Adalsteinsson E, Bell RL, Sullivan EV (2007) 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. Neuropsychopharmacology 32:1149–1177CrossRefGoogle Scholar
- Pfefferbaum A, Rosenbloom MJ, Sassoon SA, Kemper CA, Deresinski S, Rohlfing T, Sullivan EV (2012) Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age. Biol Psychiatry 72:361–370CrossRefPubMedPubMedCentralGoogle Scholar
- Rackayova V, Braissant O, McLin VA, Berset C, Lanz B, Cudalbu C (2015) 1H and 31P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism. Metabolic Brain Disease (in press).Google Scholar
- Zahr NM, Mayer D, Vinco S, Orduna J, Luong R, Sullivan EV, Pfefferbaum A (2009a) In vivo evidence for alcohol-induced neurochemical changes in rat brain without protracted withdrawal, pronounced thiamine deficiency, or severe liver damage. Neuropsychopharmacology 34:1427–1442CrossRefPubMedGoogle Scholar
- Zahr NM, Mayer D, Rohlfing T, Hasak M, Hsu O, Vinco S, Orduna J, Sullivan EV, Pfefferbaum A (2009b) Binge ethanol induced structural and neurochemical changes in the rat brain detectable at 3T. International Society on Magnetic Resonance in Medicine, Honolulu, HAGoogle Scholar
- Zhang SX, Weilersbacher GS, Henderson SW, Corso T, Olney JW, Langlais PJ (1995) Excitotoxic cytopathology, progression, and reversibility of thiamine deficiency-induced diencephalic lesions. J Neuropathol Exp Neurol 54:255–267Google Scholar