title: Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats.
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.
authors: Division of Neurology, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Supriti
authors: S
authors: Samantaray
authors: Eric A
authors: EA
authors: Sribnick
authors: Arabinda
authors: A
authors: Das
authors: Varduhi H
authors: VH
authors: Knaryan
authors: D Denise
authors: DD
authors: Matzelle
authors: Anil V
authors: AV
authors: Yallapragada
authors: Russel J
authors: RJ
authors: Reiter
authors: Swapan K
authors: SK
authors: Ray
authors: Naren L
authors: NL
authors: Banik
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000096:biosynthesis*; D053148:Caspase 3 / Q000096:biosynthesis; D002492:Central Nervous System Depressants / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D002154:Calpain; C505410:Casp3 protein, rat; D053148:Caspase 3; D008550:Melatonin; D002118:Calcium