Open AccessM9, A Novel Region of Amino‐Nogo‐A, Attenuates Cerebral Ischemic Injury by Inhibiting NADPH Oxidase‐Derived Superoxide Production in Mice
Author(s) -
Guo Fan,
Jin WeiLin,
Li LiYa,
Song WenYing,
Wang HuiWen,
Gou XingChun,
Mi YaJing,
Wang Qiang,
Xiong Lize
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12083
Subject(s) - apocynin , nadph oxidase , neuroprotection , reactive oxygen species , oxidative stress , pharmacology , ischemia , superoxide , chemistry , apoptosis , brain ischemia , medicine , biochemistry , enzyme
Summary Aims In acute stroke, neurological damage is due to oxidative stress and neuronal apoptotic death. This study investigated whether Nogo‐A 290‐562 residues region (M9), fused to the transduction domain of the HIV trans‐activator ( TAT ) protein, is neuroprotective against cerebral ischemia and the mechanisms. Methods Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in male C57 BL /6J mice. TAT ‐M9, its mutation or vehicle was applied via intraperitoneal injection at the onset of reperfusion. The neurobehavioral scores, infarction volumes, neuronal apoptosis, and the ratio of Bax/Bcl‐2 were evaluated. Malondialdehyde ( MDA ), reactive oxygen species ( ROS ) levels, and NADPH oxidase activation were measured in the presence or absence of the NADPH oxidase inhibitor apocynin or activator tetrabromocinnamic acid ( TBCA ). Results Immunofluorescence results confirmed that TAT ‐M9 was transduced into brain parenchyma, and it significantly improved neurological behavior, reduced infarct volumes, protected neuronal cells from apoptosis, inhibited activation of NADPH oxidase, and decreased MDA and ROS contents. Furthermore, apocynin imitated the beneficial effects of TAT ‐M9, while TBCA abolished them. Conclusions Our results demonstrate that TAT ‐M9 administration attenuates cerebral ischemia by inhibiting NADPH oxidase‐mediated oxidative damage and neuronal apoptosis in mice. TAT ‐M9 may be a potential treatment for cerebrovascular disease.