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Activity-based Training on a Treadmill with Spinal Cord Injured Wistar Rats
Published on: January 16, 2019
Therapeutic Effects of Azithromycin on Spinal Cord Injury in Male Wistar Rats: A Role for Inflammatory Pathways
Ali Rismanbaf1, Khashayar Afshari2,3, Mehdi Ghasemi4
1Department of Pharmacology and Toxicology, Islamic Azad University Tehran Medical Sciences, School of Pharmacy, Tehran, Iran (the Islamic Republic of).
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.
Insights
Azithromycin (AZM) treatment improved locomotion and reduced neuropathic pain after spinal cord injury (SCI) in rats. AZM also decreased neuroinflammation by modulating macrophage polarization, suggesting its therapeutic potential for SCI.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Spinal cord injury (SCI) is associated with detrimental inflammatory responses, including macrophage/microglia imbalance.
- Azithromycin (AZM) exhibits known anti-inflammatory properties.
Purpose of the Study:
- To investigate the therapeutic potential of azithromycin (AZM) in mitigating neuroinflammation and improving functional outcomes following spinal cord injury (SCI).
Main Methods:
- Male Wistar rats underwent spinal cord compression-induced SCI.
- Groups included sham-operated, vehicle control, and AZM-treated (180 mg/kg/d for 3 days) rats.
- Locomotor function, neuropathic pain, neuroinflammation (TNF-α, IL-10), demyelination, and M1/M2 macrophage polarization were assessed over 28 days.
Main Results:
- AZM treatment significantly improved locomotor function and reduced mechanical and thermal allodynia post-SCI.
- AZM administration led to decreased TNF-α and increased IL-10 levels in spinal cord tissue.
- Neuroinflammation was reduced, evidenced by decreased M1 and increased M2 macrophage expression, and a lower M1/M2 ratio.
Conclusions:
- Azithromycin demonstrates significant therapeutic potential for spinal cord injury.
- AZM effectively reduces neuroinflammation and alleviates sensory and locomotor complications associated with SCI.
