Effects of neuroglobin overexpression on acute brain injury and long-term outcomes after focal cerebral ischemia.
OBJECTIVE
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.
Wang
Xiaoying
X
Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, 149 13th Street, Room 2411A, Charlestown, MA 02129, USA. wangxi@helix.mgh.harvard.edu
Liu
Jianxiang
J
Zhu
Haihao
H
Tejima
Emiri
E
Tsuji
Kiyoshi
K
Murata
Yoshihiro
Y
Atochin
Dmitriy N
DN
Huang
Paul L
PL
Zhang
Chenggang
C
Lo
Eng H
EH
D000208:Acute Disease / Q000628:therapy; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019610:Cytoprotection / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D018384:Oxidative Stress / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013995:Time; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D012333:RNA, Messenger; D008315:Malondialdehyde; D005914:Globins