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

Melatonin signalling in Schwann cells during neuroregeneration

“…Rateb and colleagues have shown that melatonin treatment has improved peripheral nerve regeneration in rats, in particular, nocturnal treatment with melatonin has led to better results than the daily applications ( Rateb et al, 2017 ). Another study has come to a similar conclusion, when applying melatonin to rats with injured sciatic nerves at night ( Moharrami Kasmaie et al, 2019 ). Kaya and colleagues have shown that disruption of the circadian cycle could influence nerve regeneration—rats which had been kept at a normal 12 h light/dark cycle under treatment with melatonin during daytime have responded to the therapy better than rats which had been kept at inverted light–at–night cyclicity and treated at night ( Kaya et al, 2013 ).…”

“…Rateb and colleagues could prove that rats with a sciatic nerve injury under pulsed electromagnetic field therapy had higher number and area of myelinated axons, lower g–ratio and higher S100 expression in the regenerated nerves when treated during daytime compared to night treatments ( Rateb et al, 2017 ). Furthermore, nocturnal application of melatonin has led to an increased myelination and S100 immunoreactivity in crushed sciatic nerves compared to the daily application, whereas there was no difference between both groups in immunoreactivity against the Neurofilament–200 protein ( Moharrami Kasmaie et al, 2019 ). In contrast, no regenerative difference has been observed between animal groups treated with curcumin either during the day or night ( Moharrami Kasmaie et al, 2019 ).…”

“…Furthermore, nocturnal application of melatonin has led to an increased myelination and S100 immunoreactivity in crushed sciatic nerves compared to the daily application, whereas there was no difference between both groups in immunoreactivity against the Neurofilament–200 protein ( Moharrami Kasmaie et al, 2019 ). In contrast, no regenerative difference has been observed between animal groups treated with curcumin either during the day or night ( Moharrami Kasmaie et al, 2019 ). Kaya and colleagues have stated that after sciatic nerve injury the density and thickness of myelinated fibres were higher in animals treated with melatonin and kept at a normal illumination cycle than in the animals treated with melatonin and kept at an inverted cycle, yet no quantification and statistical analysis have been provided by the authors ( Kaya et al, 2013 ).…”

“…A wide body of research conducted over the last decades has demonstrated that the circadian hormone melatonin (N-acetyl-5-methoxytryptamine) plays a significant role in oligodendrogenesis ( Breton et al, 2021 ), regulation of neural stem cell proliferation ( Gengatharan et al, 2021 ), peripheral nerve regeneration, and re–myelination after injury of the central nervous system ( Naseem and Parvez, 2014 ). Beneficial effects of melatonin on Schwann cell functions reported in vitro and during nerve regeneration ( Chang et al, 2014 ; Rateb et al, 2017 ; Moharrami Kasmaie et al, 2019 ; Tiong et al, 2020 ; Gengatharan et al, 2021 ) imply that the Schwann cells are sensitive to intrinsic/extrinsic clock alterations and render rhythmicity as a possible factor of neurorepair. However, the experimental evidence is scarce.…”

The Impact of Supplements on Recovery After Peripheral Nerve Injury: A Review of the Literature

“…In addition, it acts as an antioxidant via a direct influence on toxic radicals and through the induction of enzymes that detoxify free radicals [ 7 ]. Thirteen articles addressed the role of melatonin after PNI [ 7 , 61 - 72 ], all of which were conducted in a rat model except for two mouse studies [ 61 , 62 ]. Melatonin improved structural preservation of the myelin sheaths [ 61 ], neural regeneration [ 72 ], functional outcomes [ 7 , 65 , 67 ], nerve conduction velocity [ 65 ], Schwann cell proliferation [ 64 ], axonal regeneration [ 66 ], increased malondialdehyde [ 62 ], decreased nerve peroxidation [ 63 ], and reduced oxidative stress [ 68 , 71 ].…”