Department of Neurology, Tongji Hospital, Tongji University, 389 Xincun Road, Shanghai, China.
Biol Trace Elem Res. 2012 Dec;150(1-3):242-8. doi: 10.1007/s12011-012-9455-0. Epub 2012 May 26.
Iron is a highly reactive free radical catalyst that has been shown to exacerbate oxidative stress and cell death in many neurodegenerative diseases. In this study, we produced a rat model of chronic cerebral hypoperfusion (CCH) by permanent bilateral carotid artery occlusion to investigate markers of iron and oxidative stress associated with it. We found CCH led to significant spatial memory impairment in the Morris water maze at 4 months after bilateral ligation. Iron deposition was observed in both the hippocampal CA1 area and cerebral cortex, and was correlated with localized neuronal death and increased lipid peroxidation. Western blotting revealed that the expression levels of ferritin heavy chain and the transferrin receptor were significantly elevated in hippocampus and cortex after CCH, whereas expression of iron regulatory protein 1 was significantly lower than in sham-treated rats. We conclude that localized neurodegeneration and concomitant cognitive impairments following CCH may result, at least in part, from local disruption of neuronal iron metabolism.
铁是一种高度活跃的自由基催化剂，已被证明会加剧许多神经退行性疾病中的氧化应激和细胞死亡。在这项研究中，我们通过永久性双侧颈动脉闭塞制作了慢性大脑低灌注（CCH）大鼠模型，以研究与 CCH 相关的铁和氧化应激标志物。我们发现，双侧结扎后 4 个月，大鼠在 Morris 水迷宫中出现明显的空间记忆障碍。在海马 CA1 区和大脑皮层均观察到铁沉积，且与局灶性神经元死亡和脂质过氧化增加相关。Western blot 显示，CCH 后海马和皮层中铁蛋白重链和转铁蛋白受体的表达水平显著升高，而铁调节蛋白 1 的表达水平明显低于假手术组大鼠。我们的结论是，CCH 后局部神经退行性变和伴随的认知障碍至少部分可能是由于神经元铁代谢局部紊乱所致。
