OBJECTIVE: Nodal is a member of the transforming growth factor β (TGF-β) family, which induces the activation of the cytoplasmic Smad2 and Smad3, both of which play a neuroprotective role against cerebral ischemia-reperfusion (I/R) injury. However, the role of Nodal in cerebral I/R is unclear. Thus, the aim of the present study was to shed light on the function of Nodal in cerebral I/R injury.
MATERIALS AND METHODS: Cerebral I/R injury was induced in the Sprague Dawley (SD) rats by middle cerebral artery occlusion (MCAO) and reperfusion and in murine hippocampal neuronal cells (HT22) by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The lentivirus vectors (Nodal overexpressing lentivirus vector [OE-Nodal] and the short hair RNA of Nodal [sh-Nodal]) were used to upregulate and downregulate Nodal in SD rats or cells.
RESULTS: Nodal expression increased in the cerebral I/R models and reached a peak after 12 h of reperfusion. OE-Nodal administration to the cerebral I/R rats significantly reduced the cerebral infarction volume and inhibited the brain cell apoptosis. It also increased the level of superoxide dismutase (SOD), an antioxidant enzyme, and decreased the levels of the lipid peroxides (malondialdehyde [MDA] and lactate dehydrogenase [LDH]), in addition to those of the proinflammatory factors. Consistently, the upregulation of Nodal in HT22 by OGD/R significantly increased the SOD level and decreased the levels of MDA, LDH, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α).
CONCLUSIONS: This study revealed that Nodal exerted a protective role during cerebral I/R by inhibiting excessive oxidative stress and inflammation.Free PDF Download
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To cite this article
Y. Cui, J.-Q. Wang, X.-H. Shi, Y.-Y. Wang, H.-Y. Liu, Z. Li, Y. Dong, J. Mang, Z.-X. Xu
Nodal mitigates cerebral ischemia-reperfusion injury via inhibiting oxidative stress and inflammation
Eur Rev Med Pharmacol Sci
Vol. 23 - N. 13