Sodium pyruvate reduces hypoxic-ischemic injury to neonatal rat brain.
Sodium pyruvate reduces hypoxic-ischemic injury to neonatal rat brain.
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DOI：
10.1038/pr.2012.107
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发表时间：
2012-11
影响因子：
3.6
通讯作者：
Lee, Wei-Hua
中科院分区：
文献类型：
--
作者：
Pan, Rui;Rong, Zhihui;She, Yun;Cao, Yuan;Chang, Li-Wen;Lee, Wei-Hua
新生儿缺氧缺血（HI）仍然是严重脑损伤的主要原因，并且通常与高死亡率和终身残疾有关。未成熟的大脑对缺氧缺血极其敏感，表现为线粒体神经元长期死亡。丙酮酸钠（SP）是三羧酸循环的底物和细胞外抗氧化剂，被认为是缺氧缺血性脑病（HIE）的潜在治疗方法，但其效果尚未在适当的缺氧缺血性脑病（HIE）动物模型中进行评估。这项研究采用了来自缺氧和缺糖（OGD）的新生大鼠的原代皮质神经元培养物以及完善的新生大鼠缺氧缺血模型。 HI 导致脑组织损失并损害感觉运动功能和空间记忆，而 SP 显着减少脑损伤并改善神经功能。 SP 的这些神经保护作用可能是通过维持 ATP 水平和防止细胞内活性氧 (ROS) 水平增加来改善脑代谢的结果。 SP 治疗还降低了 Bax（未成熟神经元死亡信号）的水平，阻断了 caspase-3 的激活，并在体外和体内激活了关键的生存信号激酶 Akt。 SP通过维持脑代谢和线粒体功能来保护新生儿脑免受缺氧缺血性损伤。
Neonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to hypoxia-ischemia, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy (HIE), but its effects have not been evaluated in appropriate animal models for hypoxic-ischemic encephalopathy (HIE). This investigation employed primary cortical neuron cultures derived from neonatal rats subjected to oxygen and glucose deprivation (OGD) and a well-established neonatal rat hypoxia-ischemia model. HI caused brain tissue loss and impaired sensorimotor function and spatial memory while SP significantly reduced brain damage and improved neurological performance. These neuroprotective effects of SP are likely the result of improved cerebral metabolism as demonstrated by maintaining ATP levels and preventing an increase in intracellular reactive oxygen species (ROS) levels. SP treatment also decreased levels of Bax, a death signal for immature neurons, blocked caspases-3 activation, and activated a key survival signaling kinase, Akt, both in vitro and in vivo. SP protected neonatal brain from hypoxic-ischemic injury through maintaining cerebral metabolism and mitochondrial function.
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影响因子：
1.9
作者：
Hagberg H;Mallard C;Rousset CI;Xiaoyang Wang
通讯作者：
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影响因子：
3.1
作者：
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影响因子：
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作者：
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通讯作者：
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