Dose-dependent neuroprotective effects of melatonin on experimental spinal cord injury in rats

Gül, Şanser; Çelik, Suat Erol; Kalaycı, Murat; Taşyürekli, Mustafa; Çokar, Necla; Bılge, Turgay

doi:10.1016/j.surneu.2005.03.036

Cited by 46 publications

(19 citation statements)

References 21 publications

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“…For this reason, some antioxidative treatments involving the use of pharmacologic agents such as melatonin and curcumin have been tried in the animal SCI models to reduce ROS and concomitant functional deteriorations following SCI 22. In clinical settings, methylprednisolone (MP), a well‐known anti‐inflammatory agent during acute stage, also shows some antioxidative effects at higher doses;23 however, the high dose regimen is not recommended as a standard protocol now due to the adverse effects with relatively weak evidence of clinical improvements 24.…”

Section: Resultsmentioning

confidence: 99%

Functional Recovery of Contused Spinal Cord in Rat with the Injection of Optimal‐Dosed Cerium Oxide Nanoparticles

et al. 2017

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Spinal cord injury (SCI) produces excess reactive oxygen species (ROS) that can exacerbate secondary injury and lead to permanent functional impairment. Hypothesizing that cerium oxide nanoparticles (CONPs) as an effective ROS scavenger may offset this damaging effect, it is first demonstrated in vitro that CONPs suppressed inducible nitric oxide synthase (iNOS) generation and enhanced cell viability of hydrogen peroxide (H2O2)‐insulted cortical neurons. Next, CONPs are administered at various does (50–4000 µg mL−1) to a contused spinal cord rat model and monitored the disease progression for up to eight weeks. At one day postinjury, the number of iNOS+ cells decreases in the treated groups compared with the control. At one week, the cavity size and inflammatory cells are substantially reduced, and the expression of proinflammatory and apoptotic molecules is downregulated with a concurrent upregulation of anti‐inflammatory cytokine. By eight weeks, the treated groups show significantly improved locomotor functions compared with the control. This study shows for the first time that injection of optimal‐dosed CONPs alone into contusion‐injured spinal cord of rats can reduce ROS level, attenuate inflammation and apoptosis, and consequently help locomotor functional recovery, adding a promising and complementary strategy to the other treatments of acute SCI.

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Section: Resultsmentioning

confidence: 99%

Functional Recovery of Contused Spinal Cord in Rat with the Injection of Optimal‐Dosed Cerium Oxide Nanoparticles

et al. 2017

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“…Gül et al reported the neuroprotective effects of melatonin on experimental SCI in rats 28 . The 100 mg/kg group had better outcomes than the 50 mg/kg group did.…”

Section: Discussionmentioning

confidence: 99%

Anti-edema effect of melatonin on spinal cord injury in rats

Li¹,

Yu²,

Yang³

et al. 2015

BIOMED PAP

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, Liangbi Xiang aAim. To determine the anti-edema effects of melatonin on spinal cord injury (SCI) in rats. Methods. A total of 150 adult male Sprague-Dawley rats were randomly allocated to the following three groups (n=50): a sham group which underwent laminectomy without dural compression; an SCI group, which underwent laminectomy followed by SCI and received saline i.p. immediately after injury and then daily for 2 days; an MT group, which underwent laminectomy followed by SCI and received a 100 mg/kg dose of melatonin i.p. immediately after SCI and then daily for 2 days. The cords were removed at 12, 24, 48 and 72 h after surgery in every group. Spinal cord edema was evaluated by determining the spinal cord water content. Expressions of AQP4 and GFAP positive cells in injured spinal cord were detected by immunohistochemical staining, and protein expressions of AQP4 and GFAP were detected by Western blotting. Results. Spinal cord water content was obviously increased after SCI, which was maintained almost unchanged by melatonin treatment (100 mg/kg) at 12 h after injury but was significantly reduced from 24 h to 72 h. The expressions of AQP4 and GFAP increased in the injured spinal cord segments, which were decreased by melatonin treatment (100 mg/kg) between 24 h and 72 h after SCI. Conclusions. Melatonin (100 mg/kg) had anti-edema effects after acute SCI probably by down-regulating the expression level of AQP4 protein, and it may eliminate astrocytic swelling after SCI through down-regulating the expression level of GFAP protein.

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“…In literature, it has been shown that various antioxidant agents have been used in different conditions to prevent the effects of oxidative stress. As an antioxidant agent, the effect of melatonin on oxidative stress has been shown in numerous in vivo and in vitro studies previously [27][28][29][30]. The free radical scavenger functions of melatonin in prevention of I/R injury and attenuation of the effects of reperfusion injury has been investigated in many organs such as liver, heart, kidney, testis, intestines.…”

Section: Discussionmentioning

confidence: 99%

“…Because of its high liposolubility property, melatonin penetrates all cellular membranes easily and shows its all protective effects [28] Different dose regimens and administration schemes of melatonin have been used in experimental studies. Dose regimen varied between 2.5 and 100 mg/kg and applications from one shot to daily or weekly multiple shots [29]. In most of the animal studies, melatonin has been used in a dose of multiple 10 mg/kg daily or weekly injections.…”

Section: Discussionmentioning

confidence: 99%

An animal model of ischemic priapism and the effects of melatonin on antioxidant enzymes and oxidative injury parameters in rat penis

et al. 2010

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This experimental study was designed to produce ischemia-reperfusion (I/R) injury in rat corpus cavernosum by inducing 1 h of priapism and investigating the effects of melatonin on the levels of oxidative injury parameters. Twenty-one adult male rats were randomly divided into three groups as follows; sham operated, control group (Group C): only penectomy was performed and blood (3 ml) drawn from vena cava inferior (VCI), ischemia and reperfusion group (Group I/R); priapism (1 h) + ½ h reperfusion + penectomy + blood from VCI, melatonin treatment group (Group I/R + M); priapism (1 h) + melatonin (½ h before reperfusion, 50 mg/kg, ip) + ½ h reperfusion + penectomy + blood from VCI. Priapism was induced with a vacuum erection device (cut tip of 2-cc syringe) and a rubber band was placed at the base of the erect penis. In two groups, excluding Group C, penectomies were performed after 1 h of ischemic priapism and ½ h reperfusion for biochemical analysis of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and protein carbonyl (PC) in the tissues. In all groups, about 3 ml blood was drawn from VCI to study the same parameters in systemic circulation. The results were compared statistically using one-way analysis of variance (ANOVA). As a result, in biochemical examination of penile tissues, there were significant increase in SOD, CAT activities and MDA levels in I/R group in comparison with group C (P < 0.05). With melatonin treatment, these levels were decreased closer to control levels (P < 0.05). The changes in PC levels were insignificant in penile tissues of all groups (P > 0.05). Analysis of serum in all rats revealed that the activity of SOD and the levels of MDA, NO and PC were increased in I/R group when compared with control group but with multiple comparisons only the increases in SOD activity and NO level were significant (P < 0.05). Decrease in the activity of SOD and the levels of NO and PC were significant after melatonin administration in serum of all groups (P < 0.05). The results of this study showed that experimentally induced priapism caused oxidative injury in cavernosal tissues of rats, and treatment with melatonin alleviated these effects. From the result of this experimental study, it can be extrapolated that melatonin may be used as an antioxidant agent in the treatment of ischemic priapism in the future urology practice.

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Dose-dependent neuroprotective effects of melatonin on experimental spinal cord injury in rats

Cited by 46 publications

References 21 publications

Functional Recovery of Contused Spinal Cord in Rat with the Injection of Optimal‐Dosed Cerium Oxide Nanoparticles

Functional Recovery of Contused Spinal Cord in Rat with the Injection of Optimal‐Dosed Cerium Oxide Nanoparticles

Anti-edema effect of melatonin on spinal cord injury in rats

An animal model of ischemic priapism and the effects of melatonin on antioxidant enzymes and oxidative injury parameters in rat penis

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