Melatonin reduces stress‐activated/mitogen‐activated protein kinases in spinal cord injury

Esposito, Emanuela; Genovese, Tiziana; Caminiti, Rocco; Bramantı, Placido; Meli, Rosaria; Cuzzocrea, Salvatore

doi:10.1111/j.1600-079x.2008.00633.x

Cited by 55 publications

(39 citation statements)

References 60 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, melatonin’s protective role in SCI was related to the regulation of MAPK signaling pathways and the high-mobility group box 1 protein expression (HMGB1) in mice. Melatonin treatment in SCI mice enhanced motor recovery, reduced the activation of p38 MAPK, JNK, and ERK1/2, and the expression of HMGB1 [50]. An earlier report also showed that activation of the endogenous melatonin system in the spinal cord reduced the generation, development, and maintenance of central sensitization, with a resultant inhibition of capsaicin-induced secondary mechanical allodynia and hyperalgesia [204].…”

Section: Effect Of Melatonin On Traumatic Cns Injuriesmentioning

confidence: 97%

Antiinflammatory Activity of Melatonin in Central Nervous System

Esposito

Cuzzocrea²

2010

Self Cite

346

240

View full text Add to dashboard Cite

Melatonin is mainly produced in the mammalian pineal gland during the dark phase. Its secretion from the pineal gland has been classically associated with circadian and circanual rhythm regulation. However, melatonin production is not confined exclusively to the pineal gland, but other tissues including retina, Harderian glands, gut, ovary, testes, bone marrow and lens also produce it. Several studies have shown that melatonin reduces chronic and acute inflammation. The immunomodulatory properties of melatonin are well known; it acts on the immune system by regulating cytokine production of immunocompetent cells. Experimental and clinical data showing that melatonin reduces adhesion molecules and pro-inflammatory cytokines and modifies serum inflammatory parameters. As a consequence, melatonin improves the clinical course of illnesses which have an inflammatory etiology. Moreover, experimental evidence supports its actions as a direct and indirect antioxidant, scavenging free radicals, stimulating antioxidant enzymes, enhancing the activities of other antioxidants or protecting other antioxidant enzymes from oxidative damage. Several encouraging clinical studies suggest that melatonin is a neuroprotective molecule in neurodegenerative disorders where brain oxidative damage has been implicated as a common link. In this review, the authors examine the effect of melatonin on several neurological diseases with inflammatory components, including dementia, Alzheimer disease, Parkinson disease, multiple sclerosis, stroke, and brain ischemia/reperfusion but also in traumatic CNS injuries (traumatic brain and spinal cord injury)

show abstract

Section: Effect Of Melatonin On Traumatic Cns Injuriesmentioning

confidence: 97%

Antiinflammatory Activity of Melatonin in Central Nervous System

Esposito

Cuzzocrea²

2010

Self Cite

346

240

View full text Add to dashboard Cite

show abstract

“…In previous studies, SCI has been effectively treated with 50 or 100 mg/kg melatonin [25][26][27] . Gül et al reported the neuroprotective effects of melatonin on experimental SCI in rats 28 .…”

Section: Discussionmentioning

confidence: 99%

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

Li¹,

Yu²,

Yang³

et al. 2015

BIOMED PAP

View full text Add to dashboard Cite

, 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.

show abstract

“…Furthermore, HMGB1 has been shown to be elevated in both the spinal cord tissue and the serum of rodents with spinal cord ischemic injury (53,54). Moreover, melatonin, ethyl pyruvate and hydrogen gas were found to reduce motor neuron apoptosis, improve motor dysfunction and attenuate the release of HMGB1 in rodents with SCI (51,53,54). Previous studies have implicated that HMGB1 directly induces apoptosis in neural cells (32,33), aggravates infarction volume and exacerbates the neurological deficit in transient cerebral ischemia in rats (36,55).…”

Section: Hmgb1 In Spinal Cord Injurymentioning

confidence: 99%

“…Recently, HMGB1 has been shown to be elevated in the spinal cord tissue of rodents with spinal cord compression injury and is associated with neuronal cell apoptosis (51,52). Furthermore, HMGB1 has been shown to be elevated in both the spinal cord tissue and the serum of rodents with spinal cord ischemic injury (53,54).…”

Section: Hmgb1 In Spinal Cord Injurymentioning

confidence: 99%

HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel therapy development

Kikuchi

Uchikado²,

Miura³

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB1 plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant patients. We hypothesize that inhibition of HMGB1 release rescues patients with SCI. Taken together, our findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA-mediated HMGB1 could be administered for spinal cord repair in SCI patients. Contents1. Introduction 2. HMGB1 as a therapeutic target in various diseases 3. HMGB1 in spinal cord injury 4. HMGB1 in transplantation 5. Hypothesis IntroductionOne of the most serious clinical conditions is spinal cord injury (SCI), the incidence of which has been increasing yearly (1). Spinal cord repair is a problem that has long puzzled neuroscientists (2,3). The repair of the injured human spinal cord with resultant functional recovery is one of the major challenges of contemporary neuroscience (4). Although the mortality rate of SCI has declined to less than 5%, the disability rate associated with SCI remains high (1). One of the most destructive complications after SCI is paraplegia, which has been a constant challenge in clinical medicine (1). Facilitating recovery of spinal cord structure and function after SCI is of great interest to neuroscientists (1

show abstract

Melatonin reduces stress‐activated/mitogen‐activated protein kinases in spinal cord injury

Cited by 55 publications

References 60 publications

Antiinflammatory Activity of Melatonin in Central Nervous System

Antiinflammatory Activity of Melatonin in Central Nervous System

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

HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel therapy development

Contact Info

Product

Resources

About