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.
