Wang Xiaoyang, Hagberg Henrik, Nie Chunxia, Zhu Changlian, Ikeda Tomoaki, Mallard Carina
Departments of Physiology, Clinical Neurosciences, Perinatal Center, Sahlgrenska Academy, Göteborg, Sweden.
J Neuropathol Exp Neurol. 2007 Jun;66(6):552-61. doi: 10.1097/01.jnen.0000263870.91811.6f.
Epidemiologic evidence has underlined the impact of prenatal inflammation on the development of postnatal hypoxia-ischemia (HI) brain injury. To study to what extent prenatal inflammation affects CNS vulnerability later during development, C57BL/6 mice were subjected to intrauterine injection of lipopolysaccharide (LPS) at gestational day 15. At postnatal day (PND) 5, 9, and 70, the offspring were subjected to HI. It was found that, in neonatal mice, LPS-exposed brains showed markedly enhanced brain injury after HI, whereas in adult mice, LPS exposure resulted in a significant reduction in tissue loss after HI. Reduced myelin in subcortical white matter was noticed after HI in the LPS-exposed brains at PND14 and PND75. Increased activities of nuclear factor-kappaB and caspase-3 were obtained in fetal/neonatal brain after LPS administration. Conclusions were that 1) a prenatal low dose of LPS sensitized to HI-induced brain injury in neonates but confers protection in adulthood, 2) reduced myelination is seen after prenatal LPS exposure and HI in both neonatal and adult mice despite the fact that LPS reduced total tissue loss in adult mice; and 3) nuclear factor-kappaB and caspase-3 activation early after LPS exposure may play a role in the sensitization/protection (preconditioning) effects.
流行病学证据强调了产前炎症对产后缺氧缺血性（HI）脑损伤发展的影响。为了研究产前炎症在多大程度上影响发育后期中枢神经系统的易损性，在妊娠第15天对C57BL/6小鼠进行宫内注射脂多糖（LPS）。在出生后第5天、第9天和第70天，对后代进行HI处理。结果发现，在新生小鼠中，暴露于LPS的大脑在HI后显示出明显增强的脑损伤，而在成年小鼠中，LPS暴露导致HI后组织损失显著减少。在出生后第14天和第75天，在暴露于LPS的大脑中，HI后发现皮质下白质中的髓磷脂减少。在给予LPS后，胎儿/新生小鼠大脑中核因子-κB和半胱天冬酶-3的活性增加。结论是：1）产前低剂量LPS使新生儿对HI诱导的脑损伤敏感，但在成年期具有保护作用；2）尽管LPS减少了成年小鼠的总组织损失，但在产前LPS暴露和HI后，新生和成年小鼠均出现髓鞘形成减少；3）LPS暴露后早期核因子-κB和半胱天冬酶-3的激活可能在致敏/保护（预处理）效应中起作用。
