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

Zhiyi Fan, Wanda Zhan, Xing Su, Qiqiang Xing, Xuan Yao and Jun Cai

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, γ-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 γ-Oryzanol to treat SCI in mice. Materials and Methods: Synthesize the hydrogel according to the previous method and load the appropriate concentration of γ-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 γ-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 γ-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 γ-Oryzanol-treated mice decrease. Conclusion: Although further research is warranted, we propose that γ-Oryzanol, as a relatively inexpensive dietary phytochemical, has potential clinical value.

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