Pinson Marisa R, Bake Shameena, Hurst David A, Samiya Nadia T, Sohrabji Farida, Miranda Rajesh C
Department of Neuroscience and Experimental Therapeutics, Texas A&M School of Medicine, Bryan, TX, USA.
Women's Health in Neuroscience Program, Texas A&M University School of Medicine, Bryan, TX, USA.
iScience. 2023 Sep 13;26(10):107920. doi: 10.1016/j.isci.2023.107920. eCollection 2023 Oct 20.
Prenatal alcohol exposure (PAE) impairs recovery from cerebrovascular ischemic stroke in adult rodents. Since the gut becomes dysbiotic following stroke, we assessed links between PAE and enteric portal inflammation. Adult control and PAE rat offspring received a unilateral endothelin-1-induced occlusion of the middle cerebral artery. Post-stroke behavioral disabilities and brain cytokines were assessed. Mesenteric adipose and liver transcriptomes were assessed from stroke-exposed and stroke-naive offspring. We identified, in the liver of stroke-naive animals, a moderate correlation between PAE and a gene network for inflammatory necroptosis. PAE inhibited the acute-phase brain inflammatory cytokine response to stroke. Post-stroke neurological function was correlated with an adipose gene network associated with B-lymphocyte differentiation and nuclear factor κB (NF-κB) signaling and with a liver pro-inflammatory gene network. Collectively, PAE inhibits brain inflammation but results in an inflammatory signature in enteric portal tissues after stroke, suggesting that PAE persistently and adversely impacts the gut-brain axis following adult-onset disease.
产前酒精暴露（PAE）会损害成年啮齿动物脑血管缺血性中风后的恢复。由于中风后肠道会出现微生物群失调，我们评估了PAE与肠门静脉炎症之间的联系。成年对照大鼠和PAE大鼠后代接受了内皮素-1诱导的大脑中动脉单侧闭塞。评估了中风后的行为障碍和脑内细胞因子。对暴露于中风和未暴露于中风的后代的肠系膜脂肪和肝脏转录组进行了评估。我们在未患中风动物的肝脏中发现，PAE与炎症性坏死性凋亡基因网络之间存在适度相关性。PAE抑制了中风后急性期脑内炎症细胞因子反应。中风后的神经功能与一个与B淋巴细胞分化和核因子κB（NF-κB）信号传导相关的脂肪基因网络以及一个肝脏促炎基因网络相关。总体而言，PAE抑制脑内炎症，但在中风后导致肠门静脉组织出现炎症特征，这表明PAE在成年发病疾病后持续且不利地影响肠-脑轴。
