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

Supriti Samantaray, Eric A. Sribnick, Arabinda Das, Varduhi H. Knaryan, D. Denise Matzelle, Anil V. Yallapragada, Russel J Reiter, Swapan K. Ray, Naren L. Banik

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)348-357
Number of pages10
JournalJournal of Pineal Research
Volume44
Issue number4
DOIs
StatePublished - May 2008

Fingerprint

Calpain
Melatonin
Spinal Cord Injuries
Up-Regulation
Neuroprotective Agents
Neurofilament Proteins
Spinal Cord
Wounds and Injuries
Laminectomy
DNA Nucleotidylexotransferase
Therapeutics
Intraperitoneal Injections
Neuroglia
Peptide Hydrolases
Western Blotting
Macrophages
Apoptosis
Inflammation
Neurons
Weights and Measures

Keywords

  • Apoptosis
  • Calpain
  • Macrophages
  • Melatonin
  • Neurons
  • Spinal cord injury

ASJC Scopus subject areas

  • Endocrinology

Cite this

Samantaray, S., Sribnick, E. A., Das, A., Knaryan, V. H., Matzelle, D. D., Yallapragada, A. V., ... Banik, N. L. (2008). Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats. Journal of Pineal Research, 44(4), 348-357. https://doi.org/10.1111/j.1600-079X.2007.00534.x

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

In: Journal of Pineal Research, Vol. 44, No. 4, 05.2008, p. 348-357.

Research output: Contribution to journalArticle

Samantaray, S, Sribnick, EA, Das, A, Knaryan, VH, Matzelle, DD, Yallapragada, AV, Reiter, RJ, Ray, SK & Banik, NL 2008, 'Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats', Journal of Pineal Research, vol. 44, no. 4, pp. 348-357. https://doi.org/10.1111/j.1600-079X.2007.00534.x
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. / Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats. In: Journal of Pineal Research. 2008 ; Vol. 44, No. 4. pp. 348-357.
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