Irradiated microvascular endothelial cells may induce bystander effects in neural stem cells leading to neurogenesis inhibition

Radiation-induced neurocognitive dysfunction (RIND) has attracted a lot of attention lately due to the significant improvement of the survival of cancer patients after receiving cranial radiotherapy. The detailed mechanisms are not completely understood, but extensive evidence supports an involvement of the inhibition of hippocampal neurogenesis, which may result from radiation-induced depletion of neural stem cells (NSCs) as well as the damage to neurogenic niches. As an important component of neurogenic niches, vascular cells interact with NSCs through different signaling mechanisms, which is similar to the characteristics of radiation-induced bystander effect (RIBE). But whether RIBE is involved in neurogenesis inhibition contributed by the damaged vascular cells is unknown. Thus, the purpose of the present study was to investigate the occurrence of RIBEs in non-irradiated bystander NSCs induced by irradiated bEnd.3 vascular endothelial cells in a co-culture system. The results show that compared with the NSCs cultured alone, the properties of NSCs were significantly affected after co-culture with bEnd.3 cells, and further change was induced without obvious oxidative stress and apoptosis when bEnd.3 cells were irradiated, manifesting as a reduction in the proliferation, neurosphere-forming capability and differentiation potential of NSCs. All these results suggest that the damaged vascular endothelial cells may contribute to neurogenesis inhibition via inducing RIBEs in NSCs, thus leading to RIND.