Effect of alcohol on the central nervous system to develop neurological disorder: pathophysiological and lifestyle modulation can be potential therapeutic options for alcohol-induced neurotoxication

Abstract

The central nervous system (CNS) is the major target for adverse effects of alcohol and extensively promotes the development of a significant number of neurological diseases such as stroke, brain tumor, multiple sclerosis (MS), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Excessive alcohol consumption causes severe neuro-immunological changes in the internal organs including irreversible brain injury and it also reacts with the defense mechanism of the blood-brain barrier (BBB) which in turn leads to changes in the configuration of the tight junction of endothelial cells and white matter thickness of the brain. Neuronal injury associated with malnutrition and oxidative stress-related BBB dysfunction may cause neuronal degeneration and demyelination in patients with alcohol use disorder (AUD); however, the underlying mechanism still remains unknown. To address this question, studies need to be performed on the contributing mechanisms of alcohol on pathological relationships of neurodegeneration that cause permanent neuronal damage. Moreover, alcohol-induced molecular changes of white matter with conduction disturbance in neurotransmission are a likely cause of myelin defect or axonal loss which correlates with cognitive dysfunctions in AUD. To extend our current knowledge in developing a neuroprotective environment, we need to explore the pathophysiology of ethanol (EtOH) metabolism and its effect on the CNS. Recent epidemiological studies and experimental animal research have revealed the association between excessive alcohol consumption and neurodegeneration. This review supports an interdisciplinary treatment protocol to protect the nervous system and to improve the cognitive outcomes of patients who suffer from alcohol-related neurodegeneration as well as clarify the pathological involvement of alcohol in causing other major neurological disorders.

Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review

“…The interplay between oxidative stress, neuroimmune response, and excitotoxicity in AUD leads to neurodegeneration [ 30 ]. Chronic alcohol abuse through oxidative reduction response and inflammatory activation leads to cytoskeletal destabilization of BBB integrity, which further activates astrocytes and thus finally causes BBB disruption and neuronal death [ 68 ]. Chronic alcohol intake and oxidative stress increase dopamine expression, decrease serotonin expression, and alter the gamma-aminobutyric acid (GABA) A receptor involved in glutamate hyperactivity.…”

“…Oxidative stress plays a critical underlying role in alcohol toxicity and behavioral impairments; antioxidant therapy should be an integral part of acute alcohol intoxication and AUD treatment [39] To review connections between carnitine metabolism and the pathophysiology of the AUD Alcohol use appears to impact carnitine metabolism, most clearly in the setting of alcoholic cirrhosis; an increase in plasma carnitine may be related to disordered fatty acid metabolism and oxidative stress in AUD; carnitine can be a supplementation in the treatment of AUD [66] To provide a rationale for using CBD to treat human subjects with AUD, based on the findings of experimental studies CBD reduces alcohol-related steatosis and fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, and inducing death of activated hepatic stellate cells; CBD reduces the level of alcohol drinking in animal models of AUD by reducing ethanol intake, motivation for ethanol, relapse, anxiety, and impulsivity; it reduces alcohol-related steatosis and fibrosis in the liver and reduces alcohol-related brain damage [67] To review the mechanisms of alcohol on the pathological relationships of neurodegeneration that cause permanent neuronal damage in AUD Chronic alcohol abuse through oxidative reduction response and inflammatory activation leads to cytoskeletal destabilization of BBB integrity, which further activates astrocytes and, thus, finally causes BBB disruption and neuronal death [68] To review if anxiety disorders, depression, and AUD share oxidative stress in their etiologies Animal and human studies confirm a link between oxidative stress and anxiety, depression, and AUD. Oxidative stress might also be involved in the etiology of neuropsychiatric diseases by causing accelerated telomere shortening, mitochondrial dysfunction, inflammation excitotoxicity, and influence neuronal signaling [23] To review how induction of neuroimmune genes by binge drinking increases neuronal excitability and oxidative stress, contributing to the neurobiology of AD Ethanol-induced immune gene, NOX, catalyzes the formation of ROS and superoxide and thereby increases oxidative stress; oxidative stress, by inducing innate immune genes, significantly contributes to alcoholic brain damage and alcoholic neurodegeneration [69] To review the interrelationship between H 2 S signaling and cigarette smoking or alcohol drinking…”

Toll-like receptor-mediated neuroinflammation: relevance for cognitive dysfunctions

“…Alcohol consumption Chronic alcohol abuse impairs CNS homeostasis and contributes to >200 chronic diseases, including severe forms of dementia [68]. Following ethanol intake, TLR2, TLR3, TLR4, and TLR7 expression increases in the mouse prefrontal cortex, another important area involved in cognitive function [69].…”

Analysis of the Causes, Effects, and Treatment of Alcohol Use Disorder

“…To be specific, the impact of the treatment and prevention strategies currently employed is negligible when considering public health. Screening and brief counseling are insufficiently implemented outside of the medical context, so it is important for research to investigate how a positive effect in this domain can be achieved [4]. These gaps are largely a result of issues with research design and methodology implemented in researching treatment or prevention opportunities for alcohol problems.…”