http://www.sciencedirect.com/science/article/pii/S0006295213007491
acute ischemic stroke
- a Institute of Biomedical Sciences, College of Life Science, National Chung-hsing University, Taichung, Taiwan
- b National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan
- c Departments of Biotechnology, College of Medicine and Nursing, Hung-kuang University, Taichung, Taiwan
- d Stroke and Neurovascular Disease Center, Section of Cerebrovascular Disease, Department of Neurology, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan
- e National Taipei University of Nursing and Health Science
- f Department of Martial Arts, Chinese Culture University, Taipei, Taiwan
- g Department of Chinese Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taiwan
- h Department of Bioscience Technology, Chuan-Yuan Christian University, Taoyuan, Taiwan
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2-Methoxystypandrone
(2-MS), a naphthoquinone, has been shown to display an immunomodulatory
effect in a cellular model. To explore whether 2-MS could protect mice
against cerebral ischaemic/reperfusion (I/R)-induced brain injury, we
evaluated 2-MS's protective effects on an acute ischemic stroke by
inducing a middle cerebral artery occlusion/reperfusion (MCAO) injury in
murine model. Treatment of mice that have undergone I/R injury with
2-MS (10∼100 μg/kg, i.v.) at 2 h after MCAO enhanced survival rate and
ameliorated neurological deficits, brain infarction, neural dysfunction
and massive oxidative stress, due to an enormous production of free
radicals and breakdown of blood-brain barrier (BBB) by I/R injury; this
primarily occurred with extensive infiltration of CD11b-positive
inflammatory cells and upexpression of inducible nitric oxide synthase
(iNOS), cyclooxygenase-2 and p65 nuclear factor-kappa B (NF-κB). All of
these pathological changes were diminished by 2-MS; 2-MS also
intensively limited cortical infarction and promoted upexpression of
neurodevelopmental genes near peri-infarct cortex and endogenous
neurogenesis near subgranular zone of hippocampal dentate gyrus and the
subventricular zone, most possibly by inactivation of GSK3β which in
turn upregulating β-catenin, Bcl-2 adam11 and adamts20. We conclude that
2-MS blocks inflammatory responses by impairing NF-κB signaling to
limit the inflammation and oxidative stress for preservation of BBB
integrity; 2-MS also concomitantly promotes neurodevelopmental protein
expression and endogenous neurogenesis through inactivation of GSK3β to
enhance β-catenin signaling for upexpression of neuroprotective genes
and proteins.
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