Update of cell damage mechanisms in thiamine deficiency: focus on oxidative stress, excitotoxicity and inflammation.
Thiamine deficiency (TD) is a well-established model of Wernicke's encephalopathy. Although the neurologic dysfunction and brain damage resulting from the biochemical consequences of TD is well characterized, the mechanism(s) that lead to the selective histological lesions characteristic of this disorder remain a mystery. Over the course of many years, various structural and functional changes have been identified that could lead to cell death in this disorder. However, despite a concerted effort to explain the consequences of TD in terms of these changes, our understanding of the pathophysiology of this disorder remains unclear. This review will focus on three of these processes, i.e. oxidative stress, glutamate-mediated excitotoxicity and inflammation and their role in selective vulnerability in TD. Since TD inhibits oxidative metabolism, a feature of many neurodegenerative disease states, it represents a model system with which to explore pathological mechanisms inherent in such maladies, with the potential to yield new insights into their possible treatment and prevention.
Hazell
Alan S
AS
Department of Medicine, University of Montreal, Quebec, Canada. alan.stewart.hazell@umontreal.ca
Butterworth
Roger F
RF
D000818:Animals; D001812:Blood-Brain Barrier; D001923:Brain Chemistry / Q000502:physiology; D018846:Excitatory Amino Acids / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D013832:Thiamine Deficiency / Q000473:pathology*; D014899:Wernicke Encephalopathy / Q000201:enzymology / Q000473:pathology*
D018846:Excitatory Amino Acids; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D007655:Ketoglutarate Dehydrogenase Complex