Therapeutic Effects of Azithromycin on Spinal Cord Injury in Male Wistar Rats: A Role for Inflammatory Pathways

Authors

Ali Rismanbaf, Department of Pharmacology and Toxicology, Islamic Azad University Tehran Medical Sciences, School of Pharmacy, Tehran, Iran (the Islamic Republic of).
Khashayar Afshari, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of).
Mehdi Ghasemi, Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, United States.
Abolfazl Badripour, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of).
Arvin Haj-Mirzaian, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of).
Ahmad Reza Dehpour, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of).
Hamed Shafaroodi, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of).

Document Type

Article

Publication Title

Journal of neurological surgery. Part A, Central European neurosurgery

Abstract

BACKGROUND: Inflammatory responses, including macrophages/microglia imbalance, are associated with spinal cord injury (SCI) complications. Accumulating evidence also suggests an anti-inflammatory property of azithromycin (AZM). MATERIAL AND METHODS: Male Wistar rats were subjected to T9 vertebra laminectomy. SCI was induced by spinal cord compression at this level with an aneurysmal clip for 60 seconds. They were divided into three groups: the sham-operated group and two SCI treatment (normal saline as a vehicle control vs. AZM at 180 mg/kg/d intraperitoneally for 3 days postsurgery; first dose: 30 minutes after surgery) groups. Locomotor scaling and behavioral tests for neuropathic pain were evaluated and compared through a 28-day period. At the end of the study, tissue samples were taken to assess neuroinflammatory changes and neural demyelination using ELISA and histopathologic examinations, respectively. In addition, the proportion of M1/M2 macrophage polarization was assessed by using flow cytometry. RESULTS: Post-SCI AZM treatment (180 mg/kg/d for 3 days) significantly improved locomotion (p < 0.01) and decreased sensitivity to mechanical (p < 0.01) and thermal allodynia (p < 0.001). Moreover, there was a significant tumor necrosis factor-α (TNF-α) decline (p < 0.01) and interleukin-10 (IL-10) elevation (p < 0.01) in the spinal cord tissue of the AZM-treated group compared with the control groups 28 days post-SCI. AZM significantly improved neuroinflammation as evidenced by reduction of the M1 expression, elevation of M2 macrophages, and reduction of the M1/M2 ratio in both the dorsal root ganglion and the spinal cord tissue after SCI compared with controls (p < 0.01). CONCLUSION: AZM treatment can be considered a therapeutic agent for SCI, as it could reduce neuroinflammation and SCI sensory/locomotor complications.

First Page

411

Last Page

419

DOI

10.1055/s-0041-1735854

Publication Date

9-1-2022

Recommended Citation

Rismanbaf, Ali; Afshari, Khashayar; Ghasemi, Mehdi; Badripour, Abolfazl; Haj-Mirzaian, Arvin; Dehpour, Ahmad Reza; and Shafaroodi, Hamed, "Therapeutic Effects of Azithromycin on Spinal Cord Injury in Male Wistar Rats: A Role for Inflammatory Pathways" (2022). Internal Medicine. 296.
https://scholar.bridgeporthospital.org/internal_medicine/296

Identifier

34781403 (pubmed); 10.1055/s-0041-1735854 (doi)