Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 309, Issue -, Pages 1-8Publisher
ELSEVIER
DOI: 10.1016/j.bbr.2016.04.045
Keywords
HBO-PC; Sirt1; MCAO; Nrf2; Oxidative stress
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Funding
- National Natural Science Foundation of China [81401109, 81571309, 81360193, 81560214]
- Fundamental Research Funds for the Central Universities [GK201402024]
- Natural Fund Project [1208RJZA110]
- Health Industry Research Project of Gansu Province [GSWSKY2015-01]
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Sirtuin I (Sirt1) is a class III histone deacetylase involved in neuroprotection induced by hyperbaric oxygen preconditioning (HBO-PC) in animal models of ischemia. However, the underlying mechanisms remain to be illustrated. In the present study, rats exposed to middle cerebral artery occlusion (MCAO) were used to establish an ischemic stroke model. The infarct volume ratio, neurobehavioral score, and expressions of Sirt1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (1-10-1), and superoxide dismutase 1 (SOD1) were evaluated at 7 days after reperfusion, and the level of malondialdehyde (MDA) was used to assess oxidative stress. HBO-PC increased the expression of Sirtl and reduced infarct volume ratio and neurobehavioral deficit in MCAO rats. Meanwhile, HBO-PC also increased expression of Nrf2, HO-1, and SOD1 and decreased MDA content. Furthermore, either Sirtl or Nrf2 knockdown by short interfering RNA (siRNA) inhibited the expression of Nrf2, HO-1, and SOD1 and eliminated the neuroprotective effects of HBO-PC. Taken together, the results suggest that the Nrf2/antioxidant defense pathway is involved in the long lasting neuroprotective effects of Sirtl induced by HBO-PC against transient focal cerebral ischemia. (C) 2016 Elsevier B.V. All rights reserved.
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