Sirt3 deficiency impairs neurovascular recovery in ischemic stroke

Abstract

Aims: Sirt3 is one member of the NAD+-dependent protein deacetylase family and plays crucial roles in diverse aspects of mammalian biological function. Then the role of Sirt3 on ischemia stroke is unknown. Methods: To examine the effect of Sirt3 on ischemic stroke, we performed transient middle cerebral artery occlusion (tMCAO) in adult male Sirt3 knockout (KO) and wild-type (WT) mice. Results: The level of Sirt3 in infarct region is decreased after ischemic stroke. In addition, we found that Sirt3 KO mice showed worse neurobehavioral outcome compared with WT mice, accompanied by decreased neurogenesis and angiogenesis as shown by the reduction in number of DCX+/BrdU+ cells, NeuN+/BrdU+ cells, and CD31+/BrdU+ cells in the perifocal region during recovery phase after ischemic stroke. Furthermore, Sirt3 deficiency reduced the activation of vascular endothelial growth factor (VEGF), AKT, and extracellular signal-regulated kinases (ERK) signaling pathways. Conclusion: Our results indicated that Sirt3 is beneficial to neurovascular and functional recovery following chronic ischemic stroke.