Osteopontin reduced hypoxia-ischemia neonatal brain injury by suppression of apoptosis in a rat pup model.
Osteopontin reduced hypoxia-ischemia neonatal brain injury by suppression of apoptosis in a rat pup model.
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DOI：
10.1161/strokeaha.110.599118
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发表时间：
2011-03
期刊：
影响因子：
8.3
通讯作者：
Zhang JH
中科院分区：
文献类型：
--
作者：
Chen W;Ma Q;Suzuki H;Hartman R;Tang J;Zhang JH
骨桥蛋白（OPN）在成年实验模型的缺血性脑损伤中具有神经保护作用，因此，我们假设OPN在缺氧缺血（HI）损伤后的未成熟大脑中会提供神经保护并改善长期神经功能。
在出生后第7天的大鼠中，通过单侧结扎右侧颈动脉然后进行缺氧（8%氧气，持续2小时）来诱导HI。在HI后1小时，将OPN（0.03微克或0.1微克）脑室内注射。在第0、4、7、11、14和21天龄的正常大鼠大脑以及HI后的同侧大脑半球中评估内源性OPN的时间表达。使用2,3,5 - 氯化三苯基四氮唑（TTC）染色、凋亡细胞死亡检测和裂解的半胱天冬酶 - 3（cleaved caspase - 3）表达来评估OPN的作用。通过莫里斯水迷宫测试评估神经功能。
大脑中的内源性OPN表达在第0天龄时最高，在发育过程中持续降低直至第21天龄。HI损伤后，内源性OPN表达增加并在48小时达到峰值。外源性OPN减少了HI损伤后7周的梗死体积并改善了神经功能结果。整合素拮抗剂阻断了OPN诱导的神经保护作用。
OPN诱导的神经保护作用与裂解的半胱天冬酶 - 3抑制和抗凋亡细胞死亡有关。OPN治疗改善了新生儿HI脑损伤后的长期神经功能。
Osteopontin (OPN) is neuroprotective in ischemic brain injuries in adult experimental models, therefore, we hypothesized that OPN would provide neuroprotection and improve long term neurological function in the immature brain after hypoxic-ischemic (HI) injury. HI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8% O2 for 2h) in postnatal day 7 rats. OPN (0.03 µg or 0.1 µg) was injected intracerebroventricularly at 1h post HI. Temporal expression of endogenous OPN was evaluated in the normal rat brain at the age of day 0, 4, 7, 11, 14, and 21, and in the ipsilateral hemisphere following HI. The effects of OPN were evaluated using TTC staining, apoptotic cell death assay, and cleaved caspase-3 expression. Neurological function was assessed by Morris water maze test. Endogenous OPN expression in the brain was the highest at the age of day 0, with continuous reduction till the age of day 21 during development. After HI injury, endogenous OPN expression was increased and peaked at 48h. Exogenous OPN decreased infarct volume and improved neurological outcomes 7 weeks after HI injury. OPN-induced neuroprotection was blocked by an integrin antagonist. OPN-induced neuroprotection was associated with cleaved-caspase-3 inhibition and antiapoptotic cell death. OPN treatment improved long-term neurological function against neonatal HI brain injury.