Bone marrow mesenchymal stem cell transplantation exerts neuroprotective effects following cerebral ischemia/reperfusion injury by inhibiting autophagy via the PI3K/Akt pathway

Abstract

Although cerebral ischemia itself is associated with a high rate of disability, secondary cerebral ischemia/reperfusion (I/R) injury following recanalization is associated with much more severe outcomes. The mechanisms underlying cerebral I/R injury are complex, involving neuronal death caused by apoptosis and autophagy. Autophagy is critical for cell survival and plays an important role in the pathogenesis of cerebral I/R injury. Research has indicated that transplantation of bone marrow mesenchymal stem cells (BMSCs) is effective in repairing and reconstructing brain tissue, and that this effect may be associated with the regulation of autophagy. To explore this hypothesis, we intravenously transplanted BMSCs into a rat model of cerebral I/R injury (middle cerebral artery occlusion [MCAO]). Our results indicated that BMSCs transplantation promoted behavioral recovery, reduced cerebral infarction volume, and decreased the number of apoptotic cells in rats exposed to cerebral I/R injury. Moreover, this effect was associated with reduced expression of the autophagy-associated proteins microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1. Furthermore, BMSCs remarkably increased the expression of p-Akt and p-mTOR following cerebral I/R injury. Expression of LC3 also increased when the PI3K pathway was blocked using LY294002. In summary, our results indicated that the protective effects of BMSCs in cerebral I/R injury may be associated with the inhibition of autophagy via the activation of the PI3K/Akt/mTOR signaling pathway.

Keywords: Autophagy; BMSCs; Cerebral ischemia; PI3K/Akt; Reperfusion injury.