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Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats.

Authors
  • Samantaray, Supriti
  • Sribnick, Eric A
  • Das, Arabinda
  • Knaryan, Varduhi H
  • Matzelle, D Denise
  • Yallapragada, Anil V
  • Reiter, Russel J
  • Ray, Swapan K
  • Banik, Naren L
Type
Published Article
Journal
Journal of Pineal Research
Publisher
Wiley (Blackwell Publishing)
Publication Date
May 01, 2008
Volume
44
Issue
4
Pages
348–357
Identifiers
PMID: 18086148
Source
Medline
License
Unknown

Abstract

Multiple investigations in vivo have shown that melatonin (MEL) has a neuroprotective effect in the treatment of spinal cord injury (SCI). This study investigates the role of MEL as an intervening agent for ameliorating Ca(2+)-mediated events, including activation of calpain, following its administration to rats sustaining experimental SCI. Calpain, a Ca(2+)-dependent neutral protease, is known to be involved in the pathogenesis of SCI. Rats were injured using a standard weight-drop method that induced a moderately severe injury (40 g.cm force) at T10. Sham controls received laminectomy only. Injured animals were given either 45 mg/kg MEL or vehicle at 15 min post-injury by intraperitoneal injection. At 48 hr post-injury, spinal cord (SC) samples were collected. Immunofluorescent labelings were used to identify calpain expression in specific cell types, such as neurons, glia, or macrophages. Combination of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and double immunofluorescent labelings was used to identify apoptosis in specific cells in the SC. The effect of MEL on axonal damage was also investigated using antibody specific for dephosphorylated neurofilament protein (dNFP). Treatment of SCI animals with MEL attenuated calpain expression, inflammation, axonal damage (dNFP), and neuronal death, indicating that MEL provided neuroprotective effect in SCI. Further, expression and activity of calpain and caspse-3 were examined by Western blotting. The results indicated a significant decrease in expression and activity of calpain and caspse-3 in SCI animals after treatment with MEL. Taken together, this study strongly suggested that MEL could be an effective neuroprotective agent for treatment of SCI.

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