Effects of hypothermia on oligodendrocyte precursor cell proliferation, differentiation and maturation following hypoxia ischemia in vivo and in vitro
Effects of hypothermia on oligodendrocyte precursor cell proliferation, differentiation and maturation following hypoxia ischemia in vivo and in vitro
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DOI：
10.1016/j.expneurol.2013.03.015
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发表时间：
2013-09
影响因子：
5.3
通讯作者：
Man Xiong;Jin Li;Si-Min Ma;Yi Yang;Wen-Hao Zhou
中科院分区：
文献类型：
--
作者：
Man Xiong;Jin Li;Si-Min Ma;Yi Yang;Wen-Hao Zhou
缺氧缺血不仅引起灰质损伤，还会导致脑白质损伤，导致严重的神经功能障碍和死亡，治疗方法有限。动物模型和人类HI性脑损伤患者脑白质内少突胶质前体细胞(OPC)增多。然而，小OPC能够存活并成熟修复受损的白质。在这里，我们测试了亚低温对OPC增殖、分化和成熟的影响。7日龄大鼠左侧颈动脉结扎后给予8%氧气2h。将动物分为低温组(直肠温度32~33℃，48 h)和常温组(36~37℃，48 h)，分别于术后3，7，14，42d处死动物。我们的结果表明，低温成功地促进了HI后早期OL祖细胞(NG2+)及其在胼胝体(CC)中的增殖。髓鞘碱性蛋白(MBP)和蛋白脂蛋白检测表明，随着OL成熟度的增加，OL祖细胞(O4+)积累减少。(PLP)免疫组织化学染色和免疫印迹。此外，利用一种体外缺氧-缺血模型--氧糖剥夺(OGD)，我们证明了低温减少了Preol的积累，并促进了OPC的分化和成熟。进一步的数据表明，体外低温可显著抑制OPC的死亡。与常温动物相比，低温组HI后有髓轴突和动物行为均显著增加。综上所述，这些数据表明，在新生大鼠脑缺氧缺血事件中，低温具有保护OPC、促进OL成熟和髓鞘修复的作用。本研究为阐明低温对新生大鼠脑损伤后脑白质损伤的保护作用机制提供了新的思路。
Hypoxic-ischemia (HI) not only causes gray matter injury but also white matter injury, leading to severe neurological deficits and mortality, and only limited therapies exist. The white matter of animal models and human patients with HI-induced brain injury contains increased oligodendrocyte precursor cells (OPCs). However, little OPC can survive and mature to repair the injured white matter. Here, we test the effects of mild hypothermia on OPC proliferation, differentiation and maturation. Animals suffered to left carotid artery ligation followed by 8% oxygen for 2 h in 7-day-old rats. They were divided into a hypothermic group (rectal temperature 32–33 °C for 48 h) and a normothermic group (36–37 °C for 48 h), then animals were sacrificed at 3, 7, 14 and 42 days after HI surgery. Our results showed that hypothermia successfully enhanced early OL progenitors (NG2+) and its proliferation in the corpus callosum (CC) after HI. Late OL progenitor (O4+) accumulation decreased accompanied with increased OL maturation which is detected by myelin basic protein (MBP) and proteolipid protein. (PLP) immunostaining and immunoblotting in hypothermia compared to normothermia. Additionally, using an in vitro hypoxic-ischemia model-oxygen glucose deprivation (OGD), we demonstrated that hypothermia decreased preOL accumulation and promoted OPC differentiation and maturation. Further data indicated that OPC death was significantly suppressed by hypothermia in vitro. The myelinated axons and animal behavior both markedly increased in hypothermic- compared to normothermic-animals after HI. In summary, these data suggest that hypothermia has the effects to protect OPC and to promote OL maturation and myelin repair in hypoxic–ischemic events in the neonatal rat brain. This study proposed new aspects that may contribute to elucidate the mechanism of hypothermic neuroprotection for white matter injury in neonatal rat brain injury.