γ-Oryzanol Loaded Hyaluronic Acid Hydrogel Alleviates The Loss of Motor Function After Spinal Cord Injury in Mice by Inhibiting Endoplasmic Reticulum Stress

Background and Objective: Spinal cord injury (SCI) is typically the result of compressive forces on spinal cord tissue, leading to loss of motor or sensory function. As a cheap and biocompatible substance,gamma-Oryzanol has been shown to cross the blood-brain barrier and exert beneficial effects on neural tissue. Our Previous studies have demonstrated the potential of a hydrogel based on the cross-linking of oxidized hyaluronic acid (OHA) and Hyaluronic Acid-Adipic Dihydrazide (HA-ADH) for treating osteoarthritis by loading Selenium Nanoparticles (SeNPs) through a Schiff base reaction. This study investigated the use of this hydrogel loaded with gamma-Oryzanol to treat SCI in mice. Materials and Methods: Synthesize the hydrogel according to the previous method and load the appropriate concentration of gamma-Oryzanol. Mice were randomly divided into groups and treated accordingly. Within 6 weeks after surgery, we used multiple methods including Basso mouse scale (BMS) score to conduct behavioral tests and analyzed the lesion area by Hematoxylin and Eosin (H&E) staining and immunofluorescence staining. Results: The study showed that mice treated with gamma-Oryzanol showed better motor function. Observation of the lesion area showed that the inflammatory and demyelinating conditions of the injury site in the mice treated with gamma-Oryzanol improved and more axons related to motor function were preserved with less scar formation. Endoplasmic reticulum stress-related proteins in the spinal cord tissue of gamma-Oryzanol-treated mice decrease. Conclusion: Although further research is warranted, we propose that gamma-Oryzanol, as a relatively inexpensive dietary phytochemical, has potential clinical value.