The Potential Therapeutic Effects of Agmatine, Methylprednisolone, and Rapamycin on Experimental Spinal Cord Injury

Document Type : Original Article

Authors

1 .Department of Histology and Embryology, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey

2 .Department of Histology and Embryology, Faculty of Medicine, Near East University, Nicosia, Cyprus

3 .Department of Histology and Embryology, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale, Turkey

4 4.Department of Neurosurgery, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey

5 5.Department of Biochemistry, Prof. Dr. Cemil Tascioğlu City Hospital, Istanbul, Turkey

6 6.Department of Histology and Embryology, Faculty of Medicine, University of Kyrenia, Kyrenia, Cyprus

7 7.Department of Physiology, Faculty of Medicine, Istanbul Atlas University, Istanbul, Turkey

Abstract

Objective
In spinal cord injury (SCI), the primary mechanical damage leads to a neuroinflammatory response and the secondary neuronal injury occurs in response to the release of reactive oxygen species (ROS). In addition to the suppression of inflammation, autophagy plays a significant role in the survival of neurons during secondary SCI. The present study aimed to examine the anti-inflammatory and autophagic effects of agmatine and rapamycin in SCI and to compare the results with methylprednisolone (MP) used in the clinic.
Materials and Methods
In this animal-based experimental study, thirty adult male Sprague-Dawley rats were randomly divided into five groups as sham-control, injury, injury+MP, injury+rapamycin, injury+agmatine groups. SCI was induced by compressing the T7-8-9 segments of the spinal cord, using an aneurysm clip for one minute, and then rats were treated daily for 7 days. Seven days post-treatment, damaged spinal cord tissues of sacrificed rats were collected for microscopic and biochemical examinations using histopathologic and transmission electron microscope (TEM) scores. Malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were spectrophotometrically measured.
Results
The results of this study showed that the damaged area was smaller in the rapamycin group when compared to the MP group. Many autophagic vacuoles and macrophages were observed in the rapamycin group. Degeneration of axon, myelin, and wide edema was observed in SCI by electron microscopic observations. Fragmented myelin lamellae and contracted axons were also noted. While MDA and GPx levels were increased in the injury group, MDA levels were significantly decreased in the agmatine and MP groups, and GPx levels were decreased in the rapamycin group.
Conclusion
The results of our study confirmed that rapamycin and agmatine can be an effective treatment for secondary injury of SCI.

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