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

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Author(s): Sajad Fakhri*, Amir Kiani, Cyrus Jalili, Fatemeh Abbaszadeh, Sana Piri, Mohammad Hosein Farzaei, Mohsen Rastegari-Pouyani, Ehsan Mohammadi-Noori, Haroon Khan*

Journal Name: Current Molecular Pharmacology

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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 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, RatSpinal cord injury, Melatonin, Neuropathic Pain, Motor dysfunction, Inflammation, Rat

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(E-pub Ahead of Print)
DOI: 10.2174/1874467213666201230101811
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