Hyaluronan tetrasaccharide exerts neuroprotective effect and promotes functional recovery after acute spinal cord injury in rats.

The objective of this study was to explore the therapeutic efficiency of hyaluronan tetrasaccharide (HA4) treatment after spinal cord injury (SCI) in rats and to investigate the underlying mechanism. Locomotor functional and electrophysiological evaluations revealed that the behavioral function of rats in the HA4-treated group was significantly improved compared with the vehicle-treated group. The expression of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), cluster determinant (CD44) and Toll-like receptor-4 (TLR-4) was obviously upregulated in the HA4-treated group than that in the sham and vehicle-treated group. Furthermore, HA4 could induce BDNF and VEGF expression in the astrocytes in vitro. In addition, the high expression of BDNF and VEGF could be inhibited by blocking CD44 and TLR-4. These findings indicate that HA4 could be useful as a promising therapeutic agent for SCI and might exert the effect by interaction with the CD44 and TLR-4.