Thymosin beta 4 attenuates oxidative stress-induced injury of spinal cord-derived neural stem/progenitor cells through the TLR4/MyD88 pathway

Neural stem/progenitor cells (NSPCs) can enhance regeneration after spinal cord injury (SCI), but survival of transplanted cells remains poor. Understanding how NSPCs respond to the chemical mediators of secondary injury thus is essential for treating SCI. Thymosin beta 4 (T beta 4) has physiological functions that are highly relevant to SCI. We exposed NSPCs to oxidative stress and found reduced expression of T beta 4 in H2O2-injured NSPCs. Using an MTT assay, we found that T beta 4 dose dependently increased viability of the injured NSPCs. T beta 4 also reversed the decreases of intracellular Ca2+ concentration and increases of lactate dehydrogenase in NSPCs induced by H2O2 treatment. H2O2 exposure increased NSPC apoptosis, which T beta 4 decreased. In H2O2-induced NSPCs, ROS production and pro-inflammatory cytokines increased, and again, T beta 4 reversed these effects. We investigated the toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) signaling pathway as an underlying mechanism in T beta 4's protective effect on H2O2-exposed NSPCs. Our results showed that T beta 4 reduced expression of TLR4 and MyD88. Moreover, H2O2-exposed NSPCs that were treated with the TLR4/MyD88 pathway inhibitor showed a reversal of all the effects caused by H2O2, similar to T beta 4's effects. In conclusion, our study determined that T beta 4 attenuated H2O2-induced oxidative stress injury in NSPCs via the TLR4/MyD88 pathway.