Protection of neonatal brain against hypoxic-ischemic injury through regulating apoptosis.

本研究旨在探讨血小板衍生生长因子-a受体(PDGFR-α)活化在抗缺氧缺血性脑损伤中的作用。缺氧缺血性脑损伤可导致发育中脑髓鞘形成的少突胶质细胞损伤。在分化为成熟的OL的过程中，OL先后经历了祖细胞和未成熟阶段。只有OL祖细胞表达血小板衍生生长因子-α受体(α)，其激活可导致OL增殖，但不能诱导OL分化。为探讨新生大鼠缺氧缺血性脑损伤后外周血造血祖细胞的反应及其保护作用，我们观察了新生大鼠脑缺血模型(结扎左颈总动脉并暴露于8%O2中2 h)血小板衍生生长因子受体α的表达。我们还比较了血小板衍生生长因子受体α的表达与蛋白脂蛋白和髓鞘碱性蛋白的表达，这两种蛋白是成熟OL的代表性标志。在损伤的大脑皮层，PDGF-Rα的表达水平显著升高(P<0.01)，0.5h达高峰，168h内恢复至伤前水平。免疫组织化学显示，仅在HI后72h，损伤的大脑皮层才有明显的PDGFRα表达。相比之下，假手术对照组大脑皮层未见染色。伤后168h，仅在PDGFRα免疫阳性的损伤皮质区域可见PLP和MBP免疫阳性染色。这些结果表明，仅在损伤后的大脑皮层，PDGFRα的表达迅速而短暂地增加，并可能通过调节OL前体细胞的分化而参与细胞修复或存活过程。

The aim of this study is to determine the roles of platelet-derived growth factor-a receptor (PDGF-Rα) activation against hypoxic-ischemic (HI) brain injury.Hypoxic-ischemia (HI) causes injury to oligodendrocytes (OLs), cells which create the myelin sheath in the developing brain. OLs pass successively through progenitor and immature stages during differentiation into mature OLs. Only the OL progenitors express the platelet-derived growth factor-α receptor (PDGF-Rα), whose activation results in OL proliferation, but not OL differentiation. To study the response of OL progenitors and its role in protection after neonatal HI brain injury, we investigated the expression of PDGF-Rα in a neonatal rat stroke model (combination of left common carotid artery ligation and exposure to 8%O_2 for 2 h). We also compared PDGF-Rα expression with that of proteolipid protein (PLP) and myelin basic protein (MBP), which are representative markers of mature OLs. In the damaged cerebral cortex, PDGF-Rα mRNA levels increased significantly (p<0.01) with a peak at 0.5 h after HI insult, and returned to baseline levels within 168 h post-injury. Immunohistochemistry showed clear staining of PDGF-Rα only in the injured cerebral cortex at 72 h after HI insult. In contrast, no staining was observed in the cortex of sham-operated controls. At 168 h post-insult, immunopositive staining of PLP and MBP was found only in the damaged cortical areas where the PDGF-Rα immunopositive staining had been detected. These results indicate that the expression of PDGF-Rα increases rapidly and transiently only in the injured cerebral cortex after HI insult and may play a role in cellular repair or survival processes through the regulation of OL progenitor cell differentiation.