Neuroinflammation as a neurotoxic mechanism in alcoholism: Commentary on “Increased MCP-1 and microglia in various regions of human alcoholic brain”

Abstract

Listen

Translate article

Alcoholism–the chronic and excessive consumption of alcohol–is a syndrome characterized by untoward somatic and nervous system sequelae. Often unrecognized is the extent of the neurobehavioral deficits of alcoholism and their impact on the well-being of the individual. Further, the mechanism of alcoholism-induced neuropathology is not fully understood. Among possible causative factors are neurotoxicity of the ethanol molecule itself or its metabolic products (e.g., acetaldehyde), nutritional deficiencies (e.g., B vitamins), head trauma, and repeated withdrawals. The article by He and Crews poses yet another mechanism – alcohol-induced neuroinflammation. This review of chronic alcohol consumption as a substrate of neurodegeneration provides a context for our commentary on the clinical and basic neuroscience significance of the postmortem study of human alcoholic brains by He and Crews (this issue). Toward this end, we review brain structure, function, and chemistry studies that have led to the common belief of the neurodegenerative effects of alcoholism. We attempt to distinguish between evidence for clinically detected abnormalities as attributable to permanent or transient neural damage and whether such damage is pervasive or restricted. Finally, we proffer ideas for further neuropathological studies to explicate findings from in vivo longitudinal studies conducted in human alcoholism and animal models. A perspective on the clinical significance of alcohol-induced neuroinflammation as a potential mechanism of alcohol-induced neuropathology requires an appreciation of the terms used (or misused). According to Adams and Victor (Adams and Victor, 1993), “Atrophy specifies a gradual decay and loss of neurons, leaving in their wake no degradative products and only a sparsely cellular, fibrous gliosis while degeneration refers to a more rapid process of neuronal, myelin or tissue breakdown with resulting degradative products that evoke a more vigorous reaction of phagocytosis and cellular gliosis” (page 921). Evidence for permanent loss of neurons in alcoholism is sparse, and alcohol-induced damage to brain tissue can usually be attributable to neurodegenerative rather than atrophic processes. When neuronal death does occur, it is usually considered to be necrosis, which “occurs when neurons are damaged by a trauma or metabolic injury and typically involves the concurrent death of groups of adjacent cells. Cells undergoing necrosis initially swell and their internal components, or orgenelles, break down. The cells eventually rupture and spill debris that leads to local inflammation” (page 177) (Goodlett and Horn, 2001). Figure 1 present examples of presumed acute edematous and chronic necrotic mammillary bodies of two men diagnosed with Wernicke's encephalopathy (Sullivan and Pfefferbaum, 2008) and a rat model of pyrithiamine-induced WE (Pfefferbaum, et al., 2007). Figure 1 a) Axial MR fluid attenuated inversion recovery (FLAIR) image of an acute a 35 year-old man with schizophrenia and acute nutritional deficiency-induced Wernicke's Encephalopathy (WE). Prominent are the hyperintense signals in the mammillary bodies and ...