Published Online
on April 10, 2008

A more recent version of this article appeared on June 1, 2008

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Submitted on October 1, 2007
Revised on October 29, 2007
Accepted on October 31, 2007

Effects of Neuroglobin Overexpression on Acute Brain Injury and Long-Term Outcomes After Focal Cerebral Ischemia

Xiaoying Wang MD, PhD^*; Jianxiang Liu PhD; Haihao Zhu MD, PhD; Emiri Tejima MD; Kiyoshi Tsuji MD; Yoshihiro Murata MD; Dmitriy N. Atochin PhD; Paul L. Huang MD, PhD; Chenggang Zhang PhD; and Eng H. Lo PhD

From the Neuroprotection Research Laboratory, Departments of Neurology and Radiology (X.W., J.L., H.Z., E.T., K.T., Y.M., E.H.L.), Massachusetts General Hospital and the Program in Neuroscience, Harvard Medical School, Boston, Mass; the Cardiovascular Research Center (D.N.A., P.L.H.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass; and the Department of Molecular Neurobiology (C.Z.), Beijing Institute of Radiation Medicine, Beijing, China.

^* To whom correspondence should be addressed. E-mail: wangxi{at}helix.mgh.harvard.edu.

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.

Key words: neuroglobin • neuroprotection • oxidative stress • stroke

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