Attenuation in the evolution of experimental spinal cord trauma by treatment with melatonin

Tiziana Genovese, Emanuela Mazzon, Carmelo Muià, Placido Bramanti, Angelina De Sarro, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Melatonin is the principal secretory product of the pineal gland and its role as an immumo-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and exerts protective effects in septic shock, hemorrhagic shock and inflammation. In the present study, we evaluated the effect of melatonin treatment, in a model of spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 50 g) to the dura via a four-level T5-T8 laminectomy. SCI in rats resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis (measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining). Infiltration of spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine and Poly(ADP-ribose) (PAR) in the spinal cord tissue. In contrast, the degree of (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine and PAR formation, (c) neutrophils infiltration and (d) apoptosis was markedly reduced in spinal cord tissue obtained from rats treated with melatonin (50 mg/kg i.p., 30 min before SCI, 30 min, 6 hr, 12 hr and 24 hr after SCI). In a separate set of experiment we have clearly demonstrated that melatonin treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that treatment with melatonin reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Original languageEnglish
Pages (from-to)198-208
Number of pages11
JournalJournal of Pineal Research
Volume38
Issue number3
DOIs
Publication statusPublished - Apr 2005

Fingerprint

Melatonin
Spinal Cord Injuries
Spinal Cord
Neutrophil Infiltration
Wounds and Injuries
Apoptosis
Myelitis
Poly Adenosine Diphosphate Ribose
Inflammation
Peroxynitrous Acid
Laminectomy
Pineal Gland
DNA Nucleotidylexotransferase
Hemorrhagic Shock
Recovery of Function
Septic Shock
Malondialdehyde
Surgical Instruments
Lipid Peroxidation
Peroxidase

Keywords

  • Melatonin
  • Nuclear factor-κB
  • Peroxinitrite
  • Poly-ADP-ribose synthetase
  • Secondary injury
  • Spinal cord injury
  • Tunnel coloration

ASJC Scopus subject areas

  • Endocrinology

Cite this

Attenuation in the evolution of experimental spinal cord trauma by treatment with melatonin. / Genovese, Tiziana; Mazzon, Emanuela; Muià, Carmelo; Bramanti, Placido; De Sarro, Angelina; Cuzzocrea, Salvatore.

In: Journal of Pineal Research, Vol. 38, No. 3, 04.2005, p. 198-208.

Research output: Contribution to journalArticle

Genovese, Tiziana ; Mazzon, Emanuela ; Muià, Carmelo ; Bramanti, Placido ; De Sarro, Angelina ; Cuzzocrea, Salvatore. / Attenuation in the evolution of experimental spinal cord trauma by treatment with melatonin. In: Journal of Pineal Research. 2005 ; Vol. 38, No. 3. pp. 198-208.
@article{b35a87fc95744496a6522b7b08d84771,
title = "Attenuation in the evolution of experimental spinal cord trauma by treatment with melatonin",
abstract = "Melatonin is the principal secretory product of the pineal gland and its role as an immumo-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and exerts protective effects in septic shock, hemorrhagic shock and inflammation. In the present study, we evaluated the effect of melatonin treatment, in a model of spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 50 g) to the dura via a four-level T5-T8 laminectomy. SCI in rats resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis (measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining). Infiltration of spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine and Poly(ADP-ribose) (PAR) in the spinal cord tissue. In contrast, the degree of (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine and PAR formation, (c) neutrophils infiltration and (d) apoptosis was markedly reduced in spinal cord tissue obtained from rats treated with melatonin (50 mg/kg i.p., 30 min before SCI, 30 min, 6 hr, 12 hr and 24 hr after SCI). In a separate set of experiment we have clearly demonstrated that melatonin treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that treatment with melatonin reduces the development of inflammation and tissue injury events associated with spinal cord trauma.",
keywords = "Melatonin, Nuclear factor-κB, Peroxinitrite, Poly-ADP-ribose synthetase, Secondary injury, Spinal cord injury, Tunnel coloration",
author = "Tiziana Genovese and Emanuela Mazzon and Carmelo Mui{\`a} and Placido Bramanti and {De Sarro}, Angelina and Salvatore Cuzzocrea",
year = "2005",
month = "4",
doi = "10.1111/j.1600-079X.2004.00194.x",
language = "English",
volume = "38",
pages = "198--208",
journal = "Journal of Pineal Research",
issn = "0742-3098",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Attenuation in the evolution of experimental spinal cord trauma by treatment with melatonin

AU - Genovese, Tiziana

AU - Mazzon, Emanuela

AU - Muià, Carmelo

AU - Bramanti, Placido

AU - De Sarro, Angelina

AU - Cuzzocrea, Salvatore

PY - 2005/4

Y1 - 2005/4

N2 - Melatonin is the principal secretory product of the pineal gland and its role as an immumo-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and exerts protective effects in septic shock, hemorrhagic shock and inflammation. In the present study, we evaluated the effect of melatonin treatment, in a model of spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 50 g) to the dura via a four-level T5-T8 laminectomy. SCI in rats resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis (measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining). Infiltration of spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine and Poly(ADP-ribose) (PAR) in the spinal cord tissue. In contrast, the degree of (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine and PAR formation, (c) neutrophils infiltration and (d) apoptosis was markedly reduced in spinal cord tissue obtained from rats treated with melatonin (50 mg/kg i.p., 30 min before SCI, 30 min, 6 hr, 12 hr and 24 hr after SCI). In a separate set of experiment we have clearly demonstrated that melatonin treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that treatment with melatonin reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

AB - Melatonin is the principal secretory product of the pineal gland and its role as an immumo-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and exerts protective effects in septic shock, hemorrhagic shock and inflammation. In the present study, we evaluated the effect of melatonin treatment, in a model of spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 50 g) to the dura via a four-level T5-T8 laminectomy. SCI in rats resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis (measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining). Infiltration of spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine and Poly(ADP-ribose) (PAR) in the spinal cord tissue. In contrast, the degree of (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine and PAR formation, (c) neutrophils infiltration and (d) apoptosis was markedly reduced in spinal cord tissue obtained from rats treated with melatonin (50 mg/kg i.p., 30 min before SCI, 30 min, 6 hr, 12 hr and 24 hr after SCI). In a separate set of experiment we have clearly demonstrated that melatonin treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that treatment with melatonin reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

KW - Melatonin

KW - Nuclear factor-κB

KW - Peroxinitrite

KW - Poly-ADP-ribose synthetase

KW - Secondary injury

KW - Spinal cord injury

KW - Tunnel coloration

UR - http://www.scopus.com/inward/record.url?scp=15444378210&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15444378210&partnerID=8YFLogxK

U2 - 10.1111/j.1600-079X.2004.00194.x

DO - 10.1111/j.1600-079X.2004.00194.x

M3 - Article

VL - 38

SP - 198

EP - 208

JO - Journal of Pineal Research

JF - Journal of Pineal Research

SN - 0742-3098

IS - 3

ER -