Fetal Alcohol Exposure Alters Blood Flow and Neurological Responses to Transient Cerebral Ischemia in Adult Mice.
Fetal Alcohol Exposure Alters Blood Flow and Neurological Responses to Transient Cerebral Ischemia in Adult Mice.
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DOI：
10.1111/acer.13277
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Sohrabji F
中科院分区：
文献类型：
--
作者：
Bake S;Gardner R;Tingling JD;Miranda RC;Sohrabji F
产前酒精暴露会导致身体和神经认知缺陷，统称为“胎儿酒精谱系障碍”(FASD)。尽管 FASD 与终生智力障碍有关，但人们对介导继发性心理健康和身体残疾出现的机制知之甚少。根据我们之前的数据显示，小鼠的母体乙醇暴露会导致颅内定向胎儿血流立即减少，我们假设这种暴露也会导致产前酒精暴露（PAE）成人的颅内定向血流持续改变。我们还假设，与非 PAE 成人对照相比，暴露于急性脑血管损伤的 PAE 成人会表现出更多的脑损伤和神经行为损伤。通过胃内灌胃将怀孕的C57Bl/6小鼠暴露于3g/kg乙醇或水。通过超声成像评估 3、6 和 12 个月大的 PAE 和对照成人的颈动脉、肾动脉和股动脉的血流量。为了模拟年轻人的缺血性中风，对 3 个月大的 PAE 和对照动物进行短暂的大脑中动脉闭塞 (MCAo)，随后评估行为恢复、中风梗塞体积和脑细胞因子谱。 PAE 导致成年小鼠的血液加速显着降低，与年龄相关，特别是颈动脉。单侧短暂的 MCAo 导致 PAE 和对照成人的皮质纹状体损伤相同。然而，与对照组相比，PAE 成年小鼠中风后行为恢复显着下降。我们的数据共同表明，PAE 成年小鼠表现出持续、长期的颅内血流丧失，并且由于急性发作的成人疾病（如缺血性中风）而导致脑损伤的代偿能力下降。
Prenatal alcohol exposure can result in physical and neurocognitive deficits that are collectively termed ‘Fetal Alcohol Spectrum Disorders’ (FASD). Though FASD is associated with life-long 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 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 ethanol, 3g/kg, or water by intra-gastric 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 post-stroke 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.
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影响因子：
6.1
作者：
Dobson, C. C.;Mongillo, D. L.;Brien, D. C.;Stepita, R.;Poklewska-Koziell, M.;Winterborn, A.;Holloway, A. C.;Brien, J. F.;Reynolds, J. N.
通讯作者：
Reynolds, J. N.
影响因子：
8.3
作者：
Gaillard, Romy;Rurangirwa, Akashi A.;Jaddoe, Vincent W. V.
通讯作者：
Jaddoe, Vincent W. V.
影响因子：
15.1
作者：
Bodnar, Tamara S.;Hill, Lesley A.;Weinberg, Joanne
通讯作者：
Weinberg, Joanne
影响因子：
4.8
作者：
Balden, Robyn;Selvamani, Amutha;Sohrabji, Farida
通讯作者：
Sohrabji, Farida
影响因子：
8.3
作者：
Albers, Gregory W.;Goldstein, Larry B.;Saver, Jeffrey L.
通讯作者：
Saver, Jeffrey L.