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 β4 (Tβ4) has physiological functions that are highly relevant to SCI. We exposed NSPCs to oxidative stress and found reduced expression of Tβ4 in HO-injured NSPCs. Using an MTT assay, we found that Tβ4 dose dependently increased viability of the injured NSPCs. Tβ4 also reversed the decreases of intracellular Caconcentration and increases of lactate dehydrogenase in NSPCs induced by HOtreatment. HOexposure increased NSPC apoptosis, which Tβ4 decreased. In HO-induced NSPCs, ROS production and pro-inflammatory cytokines increased, and again, Tβ4 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 Tβ4's protective effect on HO-exposed NSPCs. Our results showed that Tβ4 reduced expression of TLR4 and MyD88. Moreover, HO-exposed NSPCs that were treated with the TLR4/MyD88 pathway inhibitor showed a reversal of all the effects caused by HOsimilar to Tβ4's effects. In conclusion, our study determined that Tβ4 attenuated HO-induced oxidative stress injury in NSPCs via the TLR4/MyD88 pathway.