Bake Shameena, Gardner Rachel, Tingling Joseph D, Miranda Rajesh C, Sohrabji Farida
Women's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, College of Medicine, Bryan, Texas.
Alcohol Clin Exp Res. 2017 Jan;41(1):117-127. doi: 10.1111/acer.13277. Epub 2016 Dec 17.
Prenatal alcohol exposure (PAE) can result in physical and neurocognitive deficits that are collectively termed "fetal alcohol spectrum disorders" (FASD). Although FASD is associated with lifelong intellectual disability, the mechanisms mediating the emergence of secondary mental health and physical disabilities are poorly understood. Based on our previous data showing that maternal ethanol (EtOH) exposure in mice resulted in an immediate reduction in cranially directed fetal blood flow, we hypothesized that such exposure would also result in persistent alterations in cranially directed blood flow in the prenatally alcohol-exposed (PAE) adult. We also hypothesized that PAE adults exposed to an acute cerebrovascular insult would exhibit more brain damage and neurobehavioral impairment compared to non-PAE adult controls.
Pregnant C57BL/6 mice were exposed to EtOH, 3 g/kg, or water by intragastric gavage. Blood flow in carotid, renal, and femoral arteries was assessed by ultrasound imaging in PAE and control adults at 3, 6, and 12 months of age. To mimic ischemic stroke in young adult populations, 3-month-old PAE and control animals were subject to transient middle cerebral artery occlusion (MCAo) and subsequently assessed for behavioral recovery, stroke infarct volume, and brain cytokine profiles.
PAE resulted in a significant age-related decrease in blood acceleration in adult mice, specifically in the carotid artery. A unilateral transient MCAo resulted in equivalent cortico-striatal damage in both PAE and control adults. However, PAE adult mice exhibited significantly decreased poststroke behavioral recovery compared to controls.
Our data collectively show that PAE adult mice exhibit a persistent, long-term loss of cranially directed blood flow, and decreased capacity to compensate for brain trauma due to acute-onset adult diseases like ischemic stroke.
产前酒精暴露（PAE）可导致身体和神经认知缺陷，这些缺陷统称为“胎儿酒精谱系障碍”（FASD）。尽管FASD与终身智力残疾有关，但介导继发性心理健康和身体残疾出现的机制仍知之甚少。基于我们之前的数据表明，母体乙醇（EtOH）暴露会导致小鼠颅骨方向的胎儿血流立即减少，我们推测这种暴露也会导致产前酒精暴露（PAE）成年小鼠颅骨方向血流的持续改变。我们还推测，与非PAE成年对照组相比，暴露于急性脑血管损伤的PAE成年小鼠会表现出更多的脑损伤和神经行为障碍。
将怀孕的C57BL/6小鼠通过灌胃给予3 g/kg乙醇或水。在3、6和12月龄时，通过超声成像评估PAE和对照成年小鼠颈动脉、肾动脉和股动脉的血流。为了模拟年轻成年人群的缺血性中风，对3月龄的PAE和对照动物进行短暂性大脑中动脉闭塞（MCAo），随后评估行为恢复、中风梗死体积和脑细胞因子谱。
PAE导致成年小鼠血液加速度显著下降，尤其是在颈动脉中，且与年龄相关。单侧短暂性MCAo在PAE和对照成年小鼠中导致同等程度的皮质纹状体损伤。然而，与对照组相比，PAE成年小鼠中风后的行为恢复明显下降。
我们的数据共同表明，PAE成年小鼠表现出颅骨方向血流的持续长期丧失，以及因缺血性中风等急性成年疾病导致的脑损伤后补偿能力下降。
