Effect of melatonin loaded chitosan hydrogel on rat spinal cord injury.

Spinal cord injury (SCI) results in the demise of neural and glial cells, as well as extensive neuro- inflammation. Hydrogel formulation for prolonged release of melatonin (Mel) has demonstrated enhanced effectiveness and safety. In this study, SCI was induced in rats by contusion at the T₉ vertebrae. Chitosan (CH) /Mel hydrogel was fabricated and characterized using scanning electron microscopy (SEM) and Fourier transform infra-red to examine its specific effects on the apoptotic and histopathological markers of SCI. The scanning electron microscopy images revealed the presence of porosity in the CH/Mel hydrogel. Forty male Wistar rats were randomly divided into five groups (n = 8), including sham, control (SCI-induced treated locally with 100 µL CH hydrogel), and groups 3, 4, and 5 (treated locally immediately after SCI induction with 100 µL CH hydrogel containing 50.00, 100, and 200 mg kg^-1 Mel, respectively). The CH/Mel hydrogel at a dose of 25.00 mg mL^-1 significantly increased cell viability in the U87 cell line after 24 hr of exposure. However, at 48 and 72 hr after exposure, Bax and Bcl2 expressions were significantly increased and reduced in the SCI group, respectively, and CH/Mel hydrogel could alleviate their expressions, especially in higher doses. In addition, S100 protein expression was up-regulated in the SCI group. However, CH/Mel hydrogel down-regulated it in a dose-dependent manner. The histopathological findings demonstrated that CH/Mel hydrogel dramatically improved SCI outcomes, like vacuolar degeneration, necrosis, and severe cystic and axonal degenerations. In conclusion, CH/Mel hydrogel induced neuroprotection and it had the potential to be used as a therapeutic agent for the treatment of SCI.