Effect of melatonin loaded chitosan hydrogel on rat spinal cord injury
Volume 16, Issue 9, September 2025, Pages 537-543
Fariborz Afroozi, Ahmad Asghari, Gholamreza Abedi, Pejman Mortazavi, Hesam Uddin Hoseinzadeh
Abstract 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.
Preparation and evaluation of controlled released implant containing mesoporous selenium nanoparticles loaded with curcumin in rats with spinal cord injury
Volume 15, Issue 7, July 2024, Pages 357-367
Ehsan Lajmiri, Moosa Javdani, Pegah Khosravian, Mohammad Hashemnia, Hossein Kazemi Mehrjerdi
Abstract In this study, a controlled released delivery drug system designed and synthesized by loading curcumin and selenium nanoparticles (SeNaPs) on chitosan hydrogel, and while evaluating the physicochemical properties of the prepared drug delivery system, the tissue changes caused by the local implant of that system in rats with experimental spinal cord injury (SCI) were investigated. For this purpose, 100 adult female rats were randomly divided into five equal groups which are: Control group without any treatment for SCI, chitosan group that received chitosan hydrogel, curcumin group that received curcumin-loaded hydrogel, SeNaP group that received chitosan loaded with SeNaPs and SeNPCur group that received chitosan loaded with SeNaPs and curcumin. On the 3rd and 7th days of the study, severe infiltration of leukocytes, especially lymphocytes, as well as axon swelling and hemorrhagic necrosis at the lesion sites were observed in all groups, especially the control group. On the 7th day, the severity of these injuries decreased in the SeNPCur group and the highest number of astrocytes was observed in this group. In addition, on the 14th and 21st days of the study, the lowest severity of nerve tissue damage and the lowest presence of inflammatory cells along with the highest number of astrocytes were seen in the SeNPCur group. The glial fibrillary acidic protein study also confirmed the presence of more and significant astrocytes in the SeNPCur, curcumin and SeNP groups at different times of the study, respectively. The histopathological results showed the neuroprotective effects of chitosan hydrogel loaded with selenium and curcumin.
Immediate administration of hTERT-MSCs-IDO1-EVs reduces hypoalbuminemia after spinal cord injury
Volume 15, Issue 1, January 2024, Pages 27-34
Shiva Amanollahi, Ahmad Reza Bahrami, Azadeh Haghighitalab, Haniyeh Shaterzadeh Yazdi, Hossein Kazemi Mehrjerdi
Abstract Spinal cord injury (SCI) presents challenging and unpredictable neurological recovery. During inflammatory conditions, the amount of serum albumin and nutrition consumption decreases. Currently, it is proposed to measure serum albumin and glucose content in human or animal subjects to predict the recovery rate and the efficiency of treatments following SCI. In this study, the effect of extra-cellular vesicles (EVs) from immortalized human adipose tissue-derived mesenchymal stem cells (hTERT-MSCs) equipped with the ectopic expression of the human indoleamine 2,3-dioxygenase-1 (IDO1) gene on serum albumin and glucose levels was investigated. After pre-clearing steps of 72-hr conditioned media, small EVs (sEVs) were isolated based on the ultra-filtration method. They were encapsulated with a chitosan-based hydrogel. Five experimental groups (female rats, N = 30, ~ 230 g) were considered, including SCI, sham, hydrogel, control green fluorescent protein (GFP)-EVs and IDO1-EVs. The 60.00 µL of hydrogel or hydrogels containing 100 µg sEVs from GFP or IDO1-EVs were locally injected immediately after SCI (laminectomy of the T10 vertebra and clip compression). After 8 weeks, non-fasting serum glucose and albumin levels were measured. The results indicated that the level of serum albumin in the animals received IDO1-EVs (3.52 ± 0.04) was increased in comparison with the SCI group (3.00 ± 0.94). Also, these animals indicated higher glucose levels in their serum (250.17 ± 69.61) in comparison with SCI ones (214 ± 45.34). Although these changes were not statistically significant, they could be considered as evidence for the beneficial effects of IDO1-EVs administration in the context of SCI to reduce hypoalbuminemia and improve energy consumption. More detailed experiments are required to confirm these results.
