Recombinant PEP-1-SOD1 improves functional recovery after neural stem cell transplantation in rats with traumatic brain injury

Abstract

The transplantation of neural stem cells (NSCs) has been demonstrated as a potential treatment strategy for traumatic brain injury (TBI). Cu, Zn-superoxide dismutase (SOD1) is an important antioxidant enzyme that detoxifies intracellular reactive oxygen species, thereby protecting cells from oxidative damage. PEP-1, a peptide carrier, is able to deliver full-length native peptides or proteins into cells. Therefore, the current study investigated the effect of the transplantation of NSCs in combination with PEP-1-SOD1 for the treatment of experimental TBI in rats. Initially, the effect of PEP-1-SOD1 on the proliferation of NSCs was evaluated by MTT assay. PEP-1-SOD1 (0.5, 2.5 and 4.5 µM) significantly increased the proliferation rates of NSCs at 24, 48 and 72 h in a dose-dependent manner. PEP-1-SOD1 also promoted the differentiation of NSCs in vitro. The in vivo experiment showed that PEP-1-SOD1 in combination with NSC transplantation significantly improved the functional recovery of rats following TBI compared with NSC transplantation alone. A significant increase in brain aquaporin-4 (AQP4) mRNA and protein expression levels was observed 4 days post-TBI in PEP-1-SOD1, NSCs and PEP-1-SOD1 + NSCs groups compared with the saline group. The PEP-1-SOD1 + NSCs group showed a further increase of AQP4 mRNA and protein expression levels compared with the NSCs and PEP-1-SOD1 groups. In conclusion, the current data suggests that PEP-1-SOD1 may promote the proliferation and differentiation of NSCs, and thereby improve the functional recovery of TBI model rats following NSCs transplantation through upregulating the expression of AQP4.