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

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

Volume: 14

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

Affiliation:

• Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149,Iran

• Department of Pharmacy, Abdul Wali Khan University Mardan, 23200,Pakistan

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

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.

Cite this article as:

Fakhri Sajad *, Kiani Amir, Jalili Cyrus , Abbaszadeh Fatemeh, Piri Sana , Farzaei H. Mohammad , Rastegari-Pouyani Mohsen , Mohammadi-Noori Ehsan and Khan Haroon*, Intrathecal Administration of Melatonin Ameliorates the Neuroinflammation- Mediated Sensory and Motor Dysfunction in A Rat Model of Compression Spinal Cord Injury, Current Molecular Pharmacology 2021; 14 (4) . https://dx.doi.org/10.2174/1874467213666201230101811