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Journal of Neurorestoratology  2018, Vol. 6 Issue (1): 49-60    doi: 10.2147/JN.S140614
Melatonin and sciatic nerve injury repair: a current perspective
Zuhal Altunkaynak Berrin1,(),Delibaş Burcu2,Altun Gamze2,Gülsüm Deniz Ömür2
1. Department of Histology and Embryology, Medical Faculty, Okan University, Istanbul; Turkey
2. Department of Histology and Embryology, Medical Faculty, Ondokuz May?s University, Samsun, Turkey
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Peripheral nerve injury is an important clinical problem that can exert hazardous effects on the health of patients. For this reason, there are more studies conducted on the regeneration of the peripheral nerves via the usage of the nerves belonging to various animals with different types of lesions, ages, and by using different methods of assessment with regular follow-up. Contrary to data obtained through experimentation and clinical observation, no ideal way of treatment was found to increase the regeneration of the peripheral nerves. Finally, the effects of melatonin in the protection of peripheral nerves against trauma, especially the protection of sciatic nerve from pathological conditions, have come into attention in a wide group of scientists as there are beneficial effects of melatonin after surgery. While numerous studies indicate the melatonin’s protective effects on the pathologies of nerves, there are also studies reporting its toxic effects on peripheral nerves. Melatonin is a widespread and crucial signaling molecule due to its features of free radical scavenging and anti-oxidation at both pharmacological and physiological conditions in vivo. In this context, although there are numerous studies elaborating the effects of melatonin in various tissues, its effects on peripheral nerves was documented in only a limited number of studies. The aim of this article was to perform a review of the knowledge in the literature on the subject of mostly beneficial or hazardous effects of melatonin on the repair of the damaged peripheral nerves.

Key wordsperipheral nerve injury      melatonin      regeneration      light and electron microscopy     
Published: 26 June 2018
Corresponding Authors: Zuhal Altunkaynak Berrin     E-mail:
Cite this article:

Zuhal Altunkaynak Berrin, Delibaş Burcu, Altun Gamze, Gülsüm Deniz Ömür. Melatonin and sciatic nerve injury repair: a current perspective. Journal of Neurorestoratology, 2018, 6: 49-60.

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Notes: (A) Normal peripheral nerve view with tightly packed nerves in normal axon diameter. (B) The view of the crushed nerve 30 days after injury. Abundant number of newly formed and small axons is observed in response to nerve damage. Wallerian degeneration and macrophage-mediated phagocytosis stages have been completed and nerve self-repair initiated. Arrow, myelinated axon; arrowhead, Schwann cell; asterisk, in some of the nerves, the myelin appears to consist of two separate rings. This is caused by the section passing through a Schmidt-Lanterman cleft.">
Figure 1The light micrograph shows the Toluidine blue staining of the rat sciatic nerve in 500-nm resin-embedded sections Notes: (A) Normal peripheral nerve view with tightly packed nerves in normal axon diameter. (B) The view of the crushed nerve 30 days after injury. Abundant number of newly formed and small axons is observed in response to nerve damage. Wallerian degeneration and macrophage-mediated phagocytosis stages have been completed and nerve self-repair initiated. Arrow, myelinated axon; arrowhead, Schwann cell; asterisk, in some of the nerves, the myelin appears to consist of two separate rings. This is caused by the section passing through a Schmidt-Lanterman cleft.
Notes: (A) Normal peripheral nerve. (B) The view of the crushed nerve 30 days after injury. Sections were stained with lead citrate and uranyl acetate. Arrow, myelinated axon; arrowhead, unmyelinated axon; asterisk, newly formed myelinated axons. Bar indicates 1 mm length.">
Figure 2The electron microscopic micrograph indicates the sciatic nerve distal to the nerve crush site from a crush-injured rat Notes: (A) Normal peripheral nerve. (B) The view of the crushed nerve 30 days after injury. Sections were stained with lead citrate and uranyl acetate. Arrow, myelinated axon; arrowhead, unmyelinated axon; asterisk, newly formed myelinated axons. Bar indicates 1 mm length.
Notes: This figure shows the effect of melatonin and its metabolites on scavenging the reactive oxygen products through nonreceptor-independent actions.Abbreviations: MT1, metallothionein 1; SOD, superoxide dismutase.">
Figure 3The schema represents the receptor-dependent and receptor-independent effects of melatonin. Notes: This figure shows the effect of melatonin and its metabolites on scavenging the reactive oxygen products through nonreceptor-independent actions.Abbreviations: MT1, metallothionein 1; SOD, superoxide dismutase.
Figure 4Melatonin is an endogenously synthesized and secreted hormone by the pineal gland and possesses intense antioxidant activity.
Notes: Melatonin induces the antioxidant protection. ROS increases the NF-kB transcription and cytokines. In addition, relationship between inflammation and lipid peroxidation is explained in the schema and the role of them on apoptosis. Abbreviations: IL, interleukin; NF-kB, nuclear factor-κB; Nrf2, nuclear factor 2; ROS, reactive oxygen species; TNF, tumor necrosis factor; ICAM, intercellular adhesion molecule; SOD, superoxide dismutase; GST, glutathione S-transferase.">
Figure 5Schematic representation shows the role of NF-kB and Nrf2 pathways on the effect of melatonin on the injury. Notes: Melatonin induces the antioxidant protection. ROS increases the NF-kB transcription and cytokines. In addition, relationship between inflammation and lipid peroxidation is explained in the schema and the role of them on apoptosis. Abbreviations: IL, interleukin; NF-kB, nuclear factor-κB; Nrf2, nuclear factor 2; ROS, reactive oxygen species; TNF, tumor necrosis factor; ICAM, intercellular adhesion molecule; SOD, superoxide dismutase; GST, glutathione S-transferase.
Abbreviations: ERK, extracellular signal-regulated kinase; MEK, mitogen-activated protein kinase.">
Figure 6Schematic representation indicates the role of ErbB2 receptor on inducing the Schwann cell proliferation through Ras/Raf/MEK/ERK pathway. Abbreviations: ERK, extracellular signal-regulated kinase; MEK, mitogen-activated protein kinase.
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