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 language | English |
|---|---|
| Pages (from-to) | 198-208 |
| Number of pages | 11 |
| Journal | Journal of Pineal Research |
| Volume | 38 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Apr 2005 |
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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 journal › Article
}
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 -