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Intrathecal Administration of Melatonin Ameliorates the Neuroinflammation- Mediated Sensory and Motor Dysfunction in A Rat Model of Compression Spinal Cord Injury

[ Vol. 14 , Issue. 4 ]

Author(s):

Sajad Fakhri*, Amir Kiani, Cyrus Jalili, Fatemeh Abbaszadeh, Sana Piri, Mohammad H. Farzaei, Mohsen Rastegari-Pouyani, Ehsan Mohammadi-Noori and Haroon Khan*   Pages 646 - 657 ( 12 )

Abstract:


Background: Spinal cord injury (SCI), often characterized by sensory-motor dysfunction, is a major debilitating disorder of the central nervous system. As no useful treatment for post- SCI complications has been approved thus far, finding novel treatments is of great importance.

Objective: Considering the promising effects of melatonin (MEL) against destructive mechanisms in other models of brain damage, in the current study, we evaluated its ameliorative effects on sensory- motor outcomes, inflammatory mediators, histological changes and other post-SCI complications.

Methods: Rats in SCI and MEL groups underwent laminectomy followed by a severe compression injury by an aneurysm clip. Then, intrathecal treatment with vehicle (5% dimethyl sulfoxide) or MEL was carried out post-injury. Acetone drop, von Frey, inclined plane, and BBB tests as well as weight changes and auricle temperature, were used to evaluate the neuropathic pain, motor function, and other post-SCI complications. The effects of MEL on the activity of MMP-2 and MMP-9 were assessed using the gelatin zymography method every week till day 28 post-SCI. Histopathological assessments were performed on days 14, 21, and 28.

Results: MEL treatment resulted in decreased motor dysfunction, mechanical and cold allodynia, auricle temperature, and also ameliorated weight loss. Moreover, MEL suppressed MMP-9 activity while increasing that of MMP-2 post-SCI, indicating its anti-neuroinflammatory effects. Also, MEL significantly preserved white matter myelinated areas and the number of sensory neurons post-SCI.

Conclusion: The results suggest MEL as a promising candidate for medical therapies with advantageous effects on improving functional recovery through suppressing inflammatory mediators, and attenuating spinal tissue damages.

Keywords:

Spinal cord injury, melatonin, neuropathic pain, motor dysfunction, inflammation, rat.

Affiliation:

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Department of Neuroscience, Faculty of Advanced Technologies in Medical Sciences, Iran University of Medical Sciences, Tehran, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Department of Pharmacy, Abdul Wali Khan University Mardan, 23200

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