The immune response after hypoxia-ischemia in a mouse model of preterm brain injury.
The immune response after hypoxia-ischemia in a mouse model of preterm brain injury.
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DOI：
10.1186/s12974-014-0153-z
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发表时间：
2014-09-05
影响因子：
9.3
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Albertsson AM;Bi D;Duan L;Zhang X;Leavenworth JW;Qiao L;Zhu C;Cardell S;Cantor H;Hagberg H;Mallard C;Wang X
早产儿脑损伤主要包括脑室周围白质软化以及灰质损伤成分，这些损伤与脑瘫和认知障碍有关。炎症被认为是这些损伤的一个重要促成因素。本研究的目的是在出生后第5天（PND）的小鼠缺氧缺血（HI）诱导的早产儿脑损伤模型中检测免疫反应，该模型以局灶性白质和灰质损伤为特征。
出生后第5天的C57Bl/6小鼠通过左侧颈动脉结扎并随后暴露于10%的氧气中50分钟、70分钟或80分钟来诱导单侧HI。在HI后7天，检查白质/灰质损伤。在HI后的不同时间点，使用逆转录聚合酶链反应（RT - PCR）和免疫组织化学染色检测HI后大脑中的免疫反应。
出生后第5天的小鼠HI 70分钟诱导了局部白质损伤，伴有局灶性皮质损伤和海马萎缩，这些特征与人类婴儿早产儿脑损伤中所见的相似。HI 50分钟导致一小部分动物受伤，HI 80分钟在多个脑区产生广泛梗死。使用HI 70分钟的早产儿脑损伤模型观察到各种免疫反应，包括与辅助性T细胞（Th）1/Th17型反应相关的转录因子和细胞因子的变化、CD4 + T细胞数量增加以及髓样细胞2上表达的触发受体（TREM - 2）及其衔接蛋白12 kDa的DNAX激活蛋白（DAP12）水平升高。
我们已经在出生后第5天的小鼠中建立了一个可重复的HI模型，该模型产生与人类婴儿早产儿脑损伤相关的一致的局部白质/灰质脑损伤。这个模型为研究早产儿脑损伤提供了一个有用的工具。在HI后观察到先天性和适应性免疫反应，并且这些反应显示出强烈的促炎Th1/Th17型偏向。这些发现为未来关于早产儿脑损伤机制的研究提供了重要基础，并表明阻断Th1/Th17型免疫反应可能在早产儿脑损伤后提供神经保护。
Preterm brain injury consists primarily of periventricular leukomalacia accompanied by elements of gray-matter injury, and these injuries are associated with cerebral palsy and cognitive impairments. Inflammation is believed to be an important contributing factor to these injuries. The aim of this study was to examine the immune response in a postnatal day (PND) 5 mouse model of preterm brain injury induced by hypoxia-ischemia (HI) that is characterized by focal white and gray-matter injury. C57Bl/6 mice at PND 5 were subjected to unilateral HI induced by left carotid artery ligation and subsequent exposure to 10% O2 for 50 minutes, 70 minutes, or 80 minutes. At seven days post-HI, the white/gray-matter injury was examined. The immune responses in the brain after HI were examined at different time points after HI using RT-PCR and immunohistochemical staining. HI for 70 minutes in PND 5 mice induced local white-matter injury with focal cortical injury and hippocampal atrophy, features that are similar to those seen in preterm brain injury in human infants. HI for 50 minutes resulted in a small percentage of animals being injured, and HI for 80 minutes produced extensive infarction in multiple brain areas. Various immune responses, including changes in transcription factors and cytokines that are associated with a T-helper (Th)1/Th17-type response, an increased number of CD4+ T-cells, and elevated levels of triggering receptor expressed on myeloid cells 2 (TREM-2) and its adaptor protein DNAX activation protein of 12 kDa (DAP12) were observed using the HI 70 minute preterm brain injury model. We have established a reproducible model of HI in PND 5 mice that produces consistent local white/gray-matter brain damage that is relevant to preterm brain injury in human infants. This model provides a useful tool for studying preterm brain injury. Both innate and adaptive immune responses are observed after HI, and these show a strong pro-inflammatory Th1/Th17-type bias. Such findings provide a critical foundation for future studies on the mechanism of preterm brain injury and suggest that blocking the Th1/Th17-type immune response might provide neuroprotection after preterm brain injury.
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影响因子：
8.3
作者：
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