Human Neural Stem Cell Secretome Inhibits Neuron Heme Uptake and Ferroptosis in Intracerebral Hemorrhage through Nrf-2 Signaling Pathway

Intracerebral hemorrhage (ICH) is a common subtype of stroke with a very high mortality rate, but there is still no effective cure. Increasing evidence suggests that heme accumulation and neuronal Ferroptosis play an important role in secondary injury after intracerebral hemorrhage. Neural stem cells, as seed cells of the central nervous system, have received much attention due to their abundant paracrine product components and low immunogenicity. In this study, we focused on the protective mechanism of neural stem cell secretome (NSC-S) against neuronal Ferroptosis in ICH mouse modal using hemin induced in vitro models and collagenase type IV induced in vivo models. The results showed that NSC-S could ameliorate neurological deficits and reduce neuronal injury in ICH mouse modal. In addition, NSC-S reduced heme uptake and Ferroptosis in Hemin-treated N2a cells in vitro. NSC-S induced the activation of Nrf-2 signaling pathway. However, these effects of NSC-S were abolished by the Nrf-2 inhibitor ML385. Notably, HSPE1 in NSC-S may be associated with the protection of NSC-S against Hemin-injured neurons via the Nrf-2 signaling pathway. In summary, NSC-S protects against secondary neuronal injury in intracerebral hemorrhage via the Nrf-2 signaling pathway. And this functionality may be implemented by HSPE1.