Reducing host aldose reductase activity promotes neuronal differentiation of transplanted neural stem cells at spinal cord injury sites and facilitates locomotion recovery.

Neural stem cell (NSC) transplantation is a promising strategy for replacing lost neurons following spinal cord injury. However, the survival and differentiation of transplanted NSCs is limited, possibly owing to the neurotoxic inflammatory microenvironment. Because of the important role of glucose metabolism in M1/M2 polarization of microglia/macrophages, we hypothesized that altering the phenotype of microglia/macrophages by regulating the activity of aldose reductase (AR), a key enzyme in the polyol pathway of glucose metabolism, would provide a more beneficial microenvironment for NSC survival and differentiation.