Women's Health in Neuroscience Program, and Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University, Bryan, Texas, USA.
Alcohol Clin Exp Res. 2022 Dec;46(12):2267-2279. doi: 10.1111/acer.14952. Epub 2022 Nov 24.
Prenatal alcohol exposure (PAE) is a significant risk factor for developmental disability, although its health consequences across the lifespan are poorly understood. Here, we hypothesized that latent brain and systemic consequences of PAE influence resiliency to adult-onset neurological disease, specifically, cerebrovascular ischemic stroke.
Pregnant Sprague-Dawley rats were exposed episodically to ethanol during the fetal neurogenic period. Adult (5 months) male and female PAE and control offspring were subjected to endothelin-1-induced unilateral middle cerebral artery occlusion. In the acute injury phase outcomes including stroke volume and neurological, endocrine, and gut permeability markers were assessed. Because the effects of stroke in human populations evolve over months to years, we also assessed hippocampal- and amygdala-dependent memory function and social interaction preference up to 6 months following a stroke, in middle-aged offspring.
Prenatal alcohol exposure did not alter infarct volume, but significantly increased neurological deficits in both sexes, and impaired interhemispheric sensorimotor integration in PAE females. The IGF-1/IGFBP3 ratio, a measure of bioavailable IGF-1, was significantly reduced, while circulating levels of bacterial lipopolysaccharide, an inflammagen, were significantly increased in PAE males. In PAE females, the circulating IGF-1/IGFBP3 ratio was significantly increased and estradiol-17b levels were significantly reduced. The intestinal fatty acid binding protein, a surrogate marker of gut permeability was also significantly increased in PAE females. Longer-term deficits in hippocampal-associated memory and social interactions were observed in PAE males, while deficits in amygdala-dependent memory were observed in PAE females.
PAE contributes to adverse effects on brain health and decreased resiliency in response to a common adult-onset neurovascular disease, cerebrovascular ischemic stroke.
产前酒精暴露（PAE）是发育障碍的一个重要危险因素，尽管其对整个生命周期的健康后果知之甚少。在这里，我们假设 PAE 的潜在大脑和系统后果会影响对成年期神经疾病（特别是脑血管缺血性中风）的适应能力。
在胎儿神经发生期间，给怀孕的 Sprague-Dawley 大鼠间歇性暴露于乙醇中。成年（5 个月）雄性和雌性 PAE 和对照后代接受内皮素-1 诱导的单侧大脑中动脉闭塞。在急性损伤阶段，评估包括中风量和神经、内分泌和肠道通透性标志物在内的结果。由于中风在人类人群中的影响在数月至数年内演变，我们还评估了中风后长达 6 个月时中年后代的海马体和杏仁核依赖性记忆功能和社交互动偏好。
产前酒精暴露不会改变梗死体积，但显著增加了两性的神经缺陷，并损害了 PAE 雌性的半球间感觉运动整合。IGF-1/IGFBP3 比值，一种生物可利用 IGF-1 的衡量标准，显著降低，而循环中细菌脂多糖（一种炎症原）的水平在 PAE 雄性中显著增加。在 PAE 雌性中，循环 IGF-1/IGFBP3 比值显著增加，雌二醇-17b 水平显著降低。肠道脂肪酸结合蛋白，一种肠道通透性的替代标志物，在 PAE 雌性中也显著增加。PAE 雄性中观察到与海马体相关的记忆和社交互动的长期缺陷，而 PAE 雌性中观察到与杏仁核相关的记忆缺陷。
PAE 导致大脑健康受到不良影响，并降低了对常见成年期神经血管疾病（脑血管缺血性中风）的适应能力。
