Effects of neuroglobin overexpression on acute brain injury and long-term outcomes after focal cerebral ischemia

被引:163
作者
Wang, Xiaoying [1 ,2 ,3 ]
Liu, Jianxiang [1 ,2 ,3 ]
Zhu, Haihao [1 ,2 ,3 ]
Tejima, Emiri [1 ,2 ,3 ]
Tsuji, Kiyoshi [1 ,2 ,3 ]
Murata, Yoshihiro [1 ,2 ,3 ]
Atochin, Dmitriy N. [4 ]
Huang, Paul L. [4 ]
Zhang, Chenggang [5 ]
Lo, Eng H. [1 ,2 ,3 ]
机构
[1] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02129 USA
[2] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA
[3] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA
[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA
[5] Beijing Inst Radiat Med, Dept Mol Neurobiol, Beijing, Peoples R China
关键词
neuroglobin; neuroprotection; oxidative stress; stroke;
D O I
10.1161/STROKEAHA.107.506022
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Emerging data suggest that neuroglobin (Ngb) may protect against hypoxic/ ischemic neuronal insults. However, the underlying mechanisms in vivo and implications for long-term outcomes are still not well understood Methods-Using our newly created Ngb overexpressing transgenic (Ngb-Tg) mice, we measured brain infarction on day 1 and day 14 after transient focal cerebral ischemia and performed neurobehavioral assessments in sensorimotor deficits on days 1, 3, 7, and 14. To test the hypothesis that Ngb may play a role in reducing oxidative stress after stroke, intracellular malondialdehyde levels were measured and compared in Ngb-Tg and wild-type mice. Results-Increased Ngb mRNA and protein levels were identified in Ngb-Tg brains. Malondialdehyde levels in ischemic hemispheres of Ngb-Tg were significantly reduced compared with wild-type controls at 8 hours and 22 hours after transient focal cerebral ischemia. Compared with wild-type controls, brain infarction volumes 1 day and 14 days after transient focal cerebral ischemia were significantly reduced in Ngb-Tg mice. However, there were no significant improvements in sensorimotor deficits for up to 14 days after stroke in Ngb-Tg mice compared with wild-type controls. Conclusions-Ngb reduces tissue infarction and markers of oxidative stress after stroke. Tissue protection by overexpressing Ngb can be sustained for up to 2 weeks.
引用
收藏
页码:1869 / 1874
页数:6
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