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Comparison of melatonin and curcumin effect at the light and dark periods on regeneration of sciatic nerve crush injury in rats.

ABSTRACT: Being one of the acute clinical problems, peripheral nerve injury can bring about a number of consequences including severe disability, reduced Quality of life (QOL) and immense costs. Currently, melatonin and curcumin are widely applied because of their immunomodulatory, anti-inflammatory, neuro-protective and antioxidant properties. The present study aims to compare the effects of melatonin and curcumin during light and dark periods on sciatic nerve crush injury repair. Accordingly, rats received IP injections of curcumin (100 mg/kg) and melatonin (10 mg/kg) over two periods of light (9:00 a.m.) and dark (9:00 p.m.) for 4 weeks. In order to evaluate rats, functional (walking track analysis and electrophysiological measurements), histomorphometric and gastrocnemius muscle mass investigations were administered. No statistically significant difference was identified between dark and light curcumin groups while curcumin groups displayed better results than did melatonin groups. In addition, dark melatonin group displayed better results than the light melatonin. On the whole, this study found that melatonin and curcumin can be used to quicken neural recovery and help treat nerve injury. It was also found that better neuroregeneration or nerve regeneration was induced when rats were treated by melatonin during the dark period while effects and injection time did not correlate in curcumin application.

SUBMITTER: Moharrami Kasmaie F

PROVIDER: S-EPMC6785766 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Comparison of melatonin and curcumin effect at the light and dark periods on regeneration of sciatic nerve crush injury in rats.

Moharrami Kasmaie Farshad F Jahromi Zohreh Z Gazor Rouhollah R Zaminy Arash A

EXCLI journal 20190821

Being one of the acute clinical problems, peripheral nerve injury can bring about a number of consequences including severe disability, reduced Quality of life (QOL) and immense costs. Currently, melatonin and curcumin are widely applied because of their immunomodulatory, anti-inflammatory, neuro-protective and antioxidant properties. The present study aims to compare the effects of melatonin and curcumin during light and dark periods on sciatic nerve crush injury repair. Accordingly, rats recei ...[more]

PMID: 31611748

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Project description:BackgroundRecent experimental studies using herbal extracts have shown the possibility of peripheral nerve regeneration. This study aimed to investigate the effects of herbal extracts on peripheral nerve regeneration in a rat sciatic nerve injury model.MethodsA total of 53 rats were randomly assigned to a control group or one of four experimental groups. In all rats, the sciatic nerve was completely severed and microscopic epineural end-to-end neurorrhaphy was performed. Normal saline (2 mL) was topically applied to the site of nerve repair in the control group, whereas four different herbal extracts - 2 mL each of Astragalus mongholicus Bunge, Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, or Paeonia lactiflora Pall. - were topically applied to the site of nerve repair in each experimental group. Nerve conduction studies were performed at an average of 11.9 weeks after the operation, and conduction velocity and proximal and distal amplitudes were measured. Biopsies were performed at an average of 13.2 weeks after the initial neurorrhaphy. The quality of nerve anastomosis and perineural adhesion to the surrounding soft tissues was macroscopically evaluated. The neuroma size at the site of the neurorrhaphy was microscopically measured, whereas the size of the scar tissue was evaluated relative to the diameter of the repaired nerve.ResultsThe nerve conduction study results showed the highest nerve conduction velocity in the experimental group that used the Coptis japonica (Thunb.) Makino extract and the highest proximal and distal amplitudes in the experimental group that used the Aconitum carmichaelii Debeaux extract. Macroscopic evaluations after the second operation showed that grade 2 perineural adhesion was found in 70.8% of rats. The mean neuroma size in the Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, and Paeonia lactiflora Pall. groups showed statistically significant decreases relative to the control group. The mean scar tissue formation index in the Paeonia lactiflora Pall. group showed a statistically significant decrease relative to the control group.ConclusionsThe peripheral nerve regeneration effect of the herbal extracts was confirmed through decreased neuroma and scar tissue formation.

Project description:Background Peripheral nerve injuries (PNIs) remain one of the great clinical challenges because of their considerable long-term disability potential. Postnatal neural crest-derived multipotent stem cells, including gingiva-derived mesenchymal stem cells (GMSCs), represent a promising source of seed cells for tissue engineering and regenerative therapy of various disorders, including PNIs. Here, we generated GMSC-repopulated nerve protectors and evaluated their therapeutic effects in a crush injury model of rat sciatic nerves. Methods GMSCs were mixed in methacrylated collagen and cultured for 48 h, allowing the conversion of GMSCs into Schwann-like cells (GiSCs). The phenotype of GiSCs was verified by fluorescence studies on the expression of Schwann cell markers. GMSCs encapsulated in the methacrylated 3D-collagen hydrogel were co-cultured with THP-1-derived macrophages, and the secretion of anti-inflammatory cytokine IL-10 or inflammatory cytokines TNF-α and IL-1β in the supernatant was determined by ELISA. In addition, GMSCs mixed in the methacrylated collagen were filled into a nerve protector made from the decellularized small intestine submucosal extracellular matrix (SIS-ECM) and cultured for 24 h, allowing the generation of functionalized nerve protectors repopulated with GiSCs. We implanted the nerve protector to wrap the injury site of rat sciatic nerves and performed functional and histological assessments 4 weeks post-surgery. Results GMSCs encapsulated in the methacrylated 3D-collagen hydrogel were directly converted into Schwann-like cells (GiSCs) characterized by the expression of S-100β, p75NTR, BDNF, and GDNF. In vitro, co-culture of GMSCs encapsulated in the 3D-collagen hydrogel with macrophages remarkably increased the secretion of IL-10, an anti-inflammatory cytokine characteristic of pro-regenerative (M2) macrophages, but robustly reduced LPS-stimulated secretion of TNF-1α and IL-1β, two cytokines characteristic of pro-inflammatory (M1) macrophages. In addition, our results indicate that implantation of functionalized nerve protectors repopulated with GiSCs significantly accelerated functional recovery and axonal regeneration of crush-injured rat sciatic nerves accompanied by increased infiltration of pro-regenerative (M2) macrophages while a decreased infiltration of pro-inflammatory (M1) macrophages. Conclusions Collectively, these findings suggest that Schwann-like cells converted from GMSCs represent a promising source of supportive cells for regenerative therapy of PNI through their dual functions, neurotrophic effects, and immunomodulation of pro-inflammatory (M1)/pro-regenerative (M2) macrophages. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02947-4.

Project description:The sensorimotor and histological aspects of peripheral neuropathies were already studied by our team in two rat models: the sciatic nerve crush and the Charcot-Marie-Tooth-1A disease. In this study, we sought to highlight and compare the protein signature of these two pathological situations. Indeed, the identification of protein profiles in diseases can play an important role in the development of pharmacological targets. In fact, Charcot-Marie-Tooth-1A rats develop motor impairments that are more severe in the hind limbs. Therefore, for the first time, protein expression in sciatic nerve of Charcot-Marie-Tooth-1A rats was examined. First, distal sciatic nerves were collected from Charcot-Marie-Tooth-1A and uninjured wild-type rats aged 3 months. After protein extraction, sequential window acquisition of all theoretical fragment ion spectra liquid chromatography and mass spectrometry was employed. 445 proteins mapped to Swiss-Prot or trEMBL Uniprot databases were identified and quantified. Of these, 153 proteins showed statistically significant differences between Charcot-Marie-Tooth-1A and wild-type groups. The majority of these proteins were overexpressed in Charcot-Marie-Tooth-1A. Hierarchical clustering and functional enrichment using Gene Ontology were used to group these proteins based on their biological effects concerning Charcot-Marie-Tooth-1A pathophysiology. Second, proteomic characterization of wild-type rats subjected to sciatic nerve crush was performed sequential window acquisition of all theoretical fragment ion spectra liquid chromatography and mass spectrometry. One month after injury, distal sciatic nerves were collected and analyzed as described above. Out of 459 identified proteins, 92 showed significant differences between sciatic nerve crush and the uninjured wild-type rats used in the first study. The results suggest that young adult Charcot-Marie-Tooth-1A rats (3 months old) develop compensatory mechanisms at the level of redox balance, protein folding, myelination, and axonogenesis. These mechanisms seem insufficient to hurdle the progress of the disease. Notably, response to oxidative stress appears to be a significant feature of Charcot-Marie-Tooth-1A, potentially playing a role in the pathological process. In contrast to the first experiment, the majority of the proteins that differed from wild-type were downregulated in the sciatic nerve crush group. Functional enrichment suggested that neurogenesis, response to axon injury, and oxidative stress were important biological processes. Protein analysis revealed an imperfect repair at this time point after injury and identified several distinguishable proteins. In conclusion, we suggest that peripheral neuropathies, whether of a genetic or traumatic cause, share some common pathological pathways. This study may provide directions for better characterization of these models and/or identifying new specific therapeutic targets.

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Comparison of melatonin and curcumin effect at the light and dark periods on regeneration of sciatic nerve crush injury in rats.

Publications

Comparison of melatonin and curcumin effect at the light and dark periods on regeneration of sciatic nerve crush injury in rats.

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