Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Brazil.
Neurotoxicology. 2022 May;90:145-157. doi: 10.1016/j.neuro.2022.03.009. Epub 2022 Mar 17.
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.
孕期或哺乳期摄入乙醇会永久性地损害中枢神经系统（CNS）的发育，导致胎儿酒精谱系障碍（FASD）。FASD 是一个通用术语，涵盖了胚胎在妊娠期暴露于酒精后引起的一系列缺陷，其中胎儿酒精综合征（FAS）被认为是最严重的。FAS 的临床特征包括面部异常、身材矮小、体重低，以及中枢神经系统（CNS）结构和/或功能损伤的证据。全球 FAS 携带者的患病率约为每 10000 例活产儿中有 15 例（每年约有 119000 名 APS 患儿出生）。美国的流行病学数据显示，FAS 的发病率超过了唐氏综合征和脊柱裂等其他先天性综合征。乙醇的有害影响出现在不同的脑区，其变化取决于胚胎暴露时的神经发育剂量和时期，包括：1）小头畸形；2）皮质发育异常，脑回明显减少；3）胼胝体发育不全或发育不良；4）认知和行为缺陷（如记忆力和学习能力受损、言语困难和多动）。目前的证据表明，中枢神经系统血管特别容易受到致畸性乙醇的影响。中枢神经系统血管由与星形胶质细胞、周细胞和小胶质细胞建立密切相互作用的特化内皮细胞组成，构成血脑屏障（BBB）的神经血管单元。此外，BBB 还具有保护功能，可以防止影响中枢神经系统的物质和药物通过。BBB 的病理性改变，如妊娠期间滥用药物、先天性感染或衰老过程，会极大地改变分子结构和血管稳定性，破坏 BBB，并加重某些神经退行性和神经疾病。在这篇综述中，我们探讨了酒精暴露对 BBB 形成的影响，具体描述了乙醇在血管内皮细胞和神经胶质细胞生理学中诱导的细胞和分子事件，以及它们在中枢神经系统发育过程中的相互作用。
