The Effects of Chitosan Hydrogel Loaded With Metformin on Spinal Cord Injury Model in Rat

Objectives: Spinal cord injury (SCI) is recognized as a serious condition that leads to both primary and secondary complications. Secondary injuries exacerbate the initial phase of cell dysfunction and cell death. Current strategies remain limited in effectively addressing SCI consequences. However, there have been reports of metformin's (Met's) neuroprotective effects on the central nervous system (CNS). The potential of chitosan (CH) hydrogel containing Met to improve SCI remains unclear. Materials and Methods: Wistar rats were divided into five groups: a sham group, an SCI group (negative control, NC), and three groups receiving CH hydrogel containing 10, 50, and 100 mg/kg of Met. We fabricated the CH/Met hydrogel and characterized it using scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). We then evaluated cell viability, Bax and Bcl2 gene expression, immunohistochemistry (IHC), and histopathological changes. Results: The CH/Met hydrogel at a dose of 12.5 mg/mL significantly increased cell viability in the U87 cell line after 48 hours of exposure. The CH/Met hydrogel groups significantly modulated Bax and Bcl2 mRNA expression, particularly at doses of 50 and 100 mg/kg compared to the SCI group. Additionally, the upregulation of S10013 protein in SCI was mitigated by the CH/Met hydrogel in a dose-dependent manner. The histopathological results showed that CH/Met hydrogel significantly improved SCIinduced alterations such as vacuolar degeneration, necrosis, severe cystic and axonal degeneration. Conclusions: Our results suggest that the CH/Met hydrogel has neuroprotection effects in an SCI-induced model in rats. CH/Met hydrogel, significantly modulated histopathological changes and apoptosis-related gene expression in SCI.