Ischemic Preconditioning Induces Oligodendrogenesis in Mouse Brain: Effects of Nrf2 Deficiency

Abstract

Ischemic preconditioning (IPC) is an approach of protection against cerebral ischemia by inducing endogenous cytoprotective machinery. However, few studies in neurogenesis and oligodendrogenesis after IPC have been reported, especially the latter. The purpose of this study is to test our hypothesis that IPC may also induce cell proliferation and oligodendrogenesis in the subventricular zone and striatum, as well as to investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) on oligodendrogenesis. IPC was induced in mice by 12-min ischemia through the occlusion of the middle cerebral artery. Newly generated cells were labeled with 5-bromo-2′-deoxyuridine. Our findings demonstrated that IPC stimulated the proliferation of neural stem cells in the subventricular zone, promoted the generation of oligodendrocyte precursor cells in the striatum and corpus callosum/external capsule (CC/EC), and stimulated oligodendrocyte precursor cells differentiation into oligodendrocytes in the striatum and the CC/EC. Furthermore, we describe a crucial role for Nrf2 in IPC-induced oligodendrogenesis in the subventricular zone, striatum, and CC/EC and show for the first time that Nrf2 promoted the migration and differentiation of oligodendrocyte precursor cells into oligodendrocytes in the striatum and CC/EC. Our data imply that IPC stimulates the oligodendrogenesis in the brain and that Nrf2 signaling may contribute to the oligodendrogenesis.