One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B(1)) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD.

Chronic alcohol consumption results in structural changes to the brain. In alcoholics without coexisting thiamine deficiency or liver disease this is largely restricted to a loss of white-matter volume. When it occurs, neuronal loss is limited in anatomic distribution and only detected with quantitative techniques. This relative paucity of neurodegeneration is reflected in studies of gene and protein expression in postmortem brain where findings are subtle and discordant between studies. In alcoholics with coexisting pathologies, neuronal loss is more marked and affects a wider range of anatomic regions, especially subcortical nuclei. Although this more widespread damage may reflect a more severe drinking history, there is evidence linking thiamine deficiency and the consequences of liver disease to the pathogenesis of alcohol-related brain damage. Furthermore, a range of other factors, such as cigarette smoking and mood disorders, that are common in alcoholics, have the potential to influence studies of brain pathology and should be considered in further studies of the neuropathology of alcoholism.

Ethanol consumption during pregnancy or lactation permanently impairs the development of the central nervous system (CNS), resulting in the spectrum of fetal alcohol disorders (FASD). FASD is a general term that covers a set of deficits in the embryo caused by gestational alcohol exposure, with fetal alcohol syndrome (FAS) considered the most serious. The clinical features of FAS include facial abnormalities, short stature, low body weight, and evidence of structural and/or functional damage to the central nervous system (CNS). The prevalence of FAS carriers worldwide is about 15 for every 10,000 live births (about 119,000 children with APS born per year). Epidemiological data in the US show that the incidence of FAS exceeds other congenital syndromes such as Down syndrome and spina bifida. The deleterious effects of ethanol appear in different brain regions, varying according to the dose and period of neural development when the embryo was exposed, and include: 1) microcephaly; 2) abnormalities in cortical development, with a significant decrease in gyrification; 3) agenesis or hypoplasia of the corpus callosum; and 4) cognitive and behavioral deficits (such as impaired memory and learning, speech difficulties, and hyperactivity). Current evidence indicates that CNS blood vessels are particularly affected by teratogenic ethanol. The CNS vasculature is composed of specialized endothelial cells that establish intimate interactions with astrocytes, pericytes, and microglia, constituting the neurovascular unit of the blood-brain barrier (BBB). Together with the fact that BBB exert protective function, it can prevent the passage of substances and drugs to treat diseases that affect the CNS. Pathological changes in the BBB, such as drug abuse during pregnancy, congenital infections, or ageing processes can drastically alter the molecular structure and vascular stability, disrupting the BBB and aggravating certain neurodegenerative and neurological diseases. In this review, we address the effects of alcohol exposure on the formation of the BBB, specifically describing the cellular and molecular events induced by ethanol in the physiology of endothelial cells and glial cells, as well as their interaction during CNS development.

Background Heavy and chronic ethanol (EtOH) exposure can cause significant structural and functional damage to the adult brain. The most devastating consequence of EtOH exposure is the neurotoxicity associated with the depletion of neurons. Regulation of splice variants in the brain can modulate protein functions, which may ultimately affect behaviors associated with alcohol dependence and EtOH-mediated neurotoxicity. Since alcohol consumption is associated with neurotoxicity, it is possible that altered splicing of survival and pro-survival factors during the development of alcoholism may contribute to the neurotoxicity. Methods Primary human neurons and a neuroblastoma cell line were exposed to different concentrations of EtOH for various time periods. Cell viability and neuronal marker expression were analyzed by MTT assay and immunoblotting, respectively. Effect of EtOH exposure on splicing regulatory protein expression and alternative splicing of candidate genes were analyzed by a biochemical approach. Transcriptional activity of SRSF1 gene was determined by reporter gene analysis. Results Our results suggest that EtOH exposure to neuronal cells at 25 mM and higher concentrations are detrimental. In addition, EtOH exposure caused a dramatic reduction in serine-arginine rich splicing factor 1 (SRSF1) expression levels. Furthermore, EtOH exposure led to pre-mRNA missplicing of Mcl-1, a pro-survival member of the Bcl-2 family, by downregulating the expression levels of serine/arginine rich splicing factor 1 (SRSF1). Moreover, ectopic expression of both SRSF1 and MCL-1L isoform was able to recover EtOH-mediated neurotoxicity. Conclusions Our results suggest that ethanol exposure can lead to pre-mRNA missplicing of Mcl-1 in neuronal cells. Our results indicate that ethanol exposure of neurons leads to a decrease in the ratio of Mcl-1L/Mcl-1S by favoring pro-apoptotic Mcl-1S splicing over anti-apoptotic Mcl-1L isoform suggesting that Mcl-1S may play a crucial role in neurotoxicity associated with alcohol consumption.

Abstract Introduction ARBD is caused by chronic alcohol misuse and a deficiency of the thiamine vitamin which causes a broad range of impairments, but people with ARBD have up to a 75% of achieving some recovery. Life story work as a psychosocial therapeutic intervention is commonly used for various service user groups although it appears to be seldom considered within an ARBD context. Aim The aim of this research was to explore and identify benefits and limitations of life story work for people with ARBD. Method Using the PRISMA statement principles, systematic searches of two academic databases were conducted resulting in 10 papers to be reviewed. Results Two main themes were identified. (1) The current research on life story work for people with dementia, cognitive impairment and depressive symptoms. (2) Variations of life story work and its benefits and challenges. Discussion Evidence suggests engaging in psychosocial activities can increase wellbeing and quality of life. However, although researchers consistently advocate for a holistic approach to ARBD recovery, the promotion of life story work appears to be overlooked. Implications for practice Life story work can increase wellbeing, engagement and rapport between the person with ARBD and the facilitator as well as aiding family involvement.

Alcohol use disorder (AUD) is associated with significant structural alterations in gray and white matter of the brain, which has potential implications for cognitive and emotional functions. These alterations appear to be related to alcohol use patterns. This study aims to systematically review voxel-based morphometry studies to identify consistent patterns of gray matter and white matter alterations in patients with AUD compared to healthy control subject and explore their associations with alcohol consumption patterns. A systematic review of neuroimaging studies was conducted, analyzing gray matter (GM) and white matter (WM) differences between healthy individuals and patients with AUD. Special attention was given to the relationship between alcohol consumption variables (e.g., duration, quantity, frequency) and GM and WM volumes. AUD patients showed significant GM alterations in the right cingulate (SDM-Z = -6.013), right insula (SDM-Z = -6.088) and left Heschl gyrus (SDM-Z = -5.254) compared to healthy control subject. WM alterations were found in the corpus callosum (SDM-Z = -3.537). Meta-regressions revealed dose-dependent associations: AUDIT scores (SDM-Z = -3.143), drinks/day (SDM-Z = -3.504), lifetime drinking (SDM-Z = 3.460), and years of dependence (SDM-Z = 3.063) were each negatively correlated with regional GM volume. Earlier age at first drink was associated with WM volume in the corpus callosum (SDM-Z = 3.229). Longer abstinence was correlated with larger WM volumes. This meta-analysis underscores the associations between alcohol consumption patterns and brain structure and provides evidence of dose-dependent associations between alcohol consumption and neuroanatomical differences.

Effect of maternal alcohol consumption on nerve cell development in the offspring. The effect of prenatal alcohol exposure on nerve cell development was investigated in neurons and glial cells cultured from fetal rat brain. Neurons were grown for one week from two week-old cortical brain cells and glial cells were cultured during four weeks from new born cortical brain cells. Two situations were examined: maternal alcohol treatment before and during pregnancy and alcohol exposure only until the beginning of pregnancy. In both situations we found a delayed nerve cell maturation assessed by biochemical markers like enolase and glutamine synthetase. Alterations of lactate dehydrogenase activity and reduced superoxide dismutase activity, involved in free radicals elimination were also observed. "In vitro" addition of alcohol to the culture medium produced an additional effect showing a lower response in the prenatal alcohol exposed brain cells than in the controls. The results confirm our previous "in vivo" experiments showing long lasting effects of maternal alcohol exposure in the offspring. Published in Alcohol and alcoholism (Oxford, Oxfordshire). Supplement (1991)

Adolescence is a risky time. Teenagers take risks and seek novelty by nature, and those actions affect their health. They are more likely to die from accidents, and experimentation with psychoactive drugs is normative. A persuasive body of literature shows that substance-using adolescents are far more likely to become drug-dependent adults than those who delay experimentation until young adulthood. Moreover, there is a direct correlation between the age of initiation for alcohol or tobacco use and adult dependence on these and other drugs (1,2). Two interpretations have been proposed to explain this correlation: 1) adolescents who become drug involved are vulnerable because of the combination of inherited impulsive, risk-taking behavior, family history, and challenging social environment, which includes access to drugs, and 2) exposure of the developing brain to addictive drugs during the critical final phase of brain development causes permanent changes in the brain that render the individual more vulnerable to addiction. Although numerous studies in humans support the former possibility, an emerging body of animal studies suggests that drug action on the brain itself has persevering effects that contribute to the progression of addiction into adulthood. The article by Cass et al. (3) in the present issue addresses this possibility. The groundbreaking studies of Jay Giedd and colleagues have shown that the developing forebrain is still undergoing remarkable structural matura

Sherwin BT (1983). "In utero alcohol exposure: functional and structural brain damage". Neurobehavioral Toxicology and Teratology. 5 (3): 363–366. PMID 6877477 Fetal alcohol spectrum disorders (FASDs) are a group of conditions that can occur in a person who is exposed to alcohol during gestation. FASDS affects 7.7 out of 1000 people globally, but is highly misdiagnosed and underdiagnosed. The several forms of the condition (in order of most severe to least severe) are: fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), alcohol-related n Conduct disorder, behavioral problems, disruptive behavior, or impulsivity Developmental language disorder Hearing loss Visual impairment, including blindness or astigmatism Developmental delay, cognitive disorder, or mental deficiency Premature birth Substance dependence Congenital malformation of retina Congenital fusion of cervical vertebrae or cervical spine fusion Attention deficit hyperactivity disorder (ADHD) or otherwise impaired attention Small eye openings (blepharophimosis), or an abnormally increased distance between the eyes, or both (hypertelorism) Other FASD conditions are partial expressions of FAS, where the central nervous system shows clinical deficits. In these other FASD conditions, an individual may be at greater risk for adverse outcomes because brain damage is present without associated visual cues of poor growth or the "FAS face" that might ordinarily trigger an FASD evaluation. Such individuals may be misdiagnosed with primary mental health disorders such as ADHD or oppositional defiance disorder without appreciation that brain damage is the underlying cause of these disorders, which requires a different treatment paradigm than typical mental health disorders. While other FASD conditions may not yet be included as an ICD or DSM-IV-TR diagnosis, they nonetheless pose significant impairment in functional behavior… Two… M…

The role of alcohol-induced epigenetic modifications that predispose the fetus to metabolic dysregulation, increased susceptibility to future substance use, and long-term behavioral and cognitive impairments has received increasing attention. Fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASDs) remain underdiagnosed worldwide. As evidence continues to demonstrate that no safe level of alcohol consumption exists during pregnancy, strengthening public awareness, maternal education, and prenatal care services has become increasingly imperative. Prenatal alcohol exposure (PAE) induces distinct and reproducible histopathological alterations in multiple developing organs, including the brain, heart, liver, kidneys, lungs, eyes, limbs, and placenta. These alterations involve cellular degeneration, tissue disorganization, inflammatory infiltration, vascular abnormalities, and impaired organ architecture, arising from oxidative stress, inflammation, apoptosis, and disrupted developmental signaling during critical periods of fetal development. This narrative review provides a comprehensive synthesis of the organ-specific histopathological consequences of PAE and integrates the underlying cellular and molecular mechanisms contributing to these alterations. Future research should further elucidate the molecular basis of ethanol teratogenicity and explore potential therapeutic strategies, such as antioxidant supplementation, nutritional modulation, and neuroprotective agents. Nevertheless, complete maternal abstinence from alcohol remains the most effective preventive strategy. By integrating histopathological findings across multiple fetal organ systems within a unified developmental framework, this review offers a distinct contribution beyond existing literature focused primarily on epidemiology or diagnosis.