Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Abstract:
Vagus nerve stimulation (VNS) exerts neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury and modulates redox status, potentially through the activity of miR‐210, an important microRNA that is regulated by hypoxia‐inducible factor and Akt‐dependent pathways. The aim of this study was to determine the mechanisms of VNS‐ and miR‐210‐mediated hypoxic tolerance. Male Sprague–Dawley rats were preconditioned with a miR‐210 antagomir (A) or with an antagomir control (AC), followed by middle cerebral artery occlusion and VNS treatment. The animals were divided into eight groups: sham I/R, I/R, I/R+AC, I/R+A, sham I/R+VNS, I/R+VNS, I/R+VNS+AC, and I/R+VNS+A. Activation of the endogenous cholinergic a7 nicotinic acetylcholine receptor (a7nAchR) pathway was identified using double immunofluorescence staining. miR‐210 expression was measured by PCR. Behavioral outcomes, infarct volume, and neuronal apoptosis were observed at 24 h following reperfusion. Markers of oxidative stress were detected using ELISA. Rats treated with VNS showed increased miR‐210 expression as well as decreased apoptosis and antioxidant stress responses compared with the I/R group; these rats also showed increased p‐Akt protein expression and significantly decreased levels of cleaved caspase 3 in the ischemic penumbra, as measured by western blot and immunofluorescence analyses, respectively. Strikingly, the beneficial effects of VNS were attenuated following miR‐210 knockdown. In conclusion, our results indicate that miR‐210 is a potential mediator of VNS‐induced neuroprotection against I/R injury. Our study highlights the neuroprotective potential of VNS, which, to date, has been largely unexplored.
