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Updated: Jan 2, 2026
Author Spotlight: Insight Into Innovations in Spinal Cord Injury Research
Published on: January 19, 2024
Delayed Azithromycin Treatment Improves Recovery After Mouse Spinal Cord Injury
Timothy J Kopper1, Katelyn E McFarlane1, William M Bailey1
1Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY, United States.
Abstract:
After spinal cord injury (SCI), macrophages infiltrate into the lesion and can adopt a wide spectrum of activation states. However, the pro-inflammatory, pathological macrophage activation state predominates and contributes to progressive neurodegeneration. Azithromycin (AZM), an FDA approved macrolide antibiotic, has been demonstrated to have immunomodulatory properties in a variety of inflammatory conditions. Indeed, we previously observed that post-SCI AZM treatment reduces pro-inflammatory macrophage activation. Further, a combined pre- and post-injury treatment paradigm improved functional recovery from SCI. Therefore, for the current study, we hypothesize that post-injury AZM treatment will improve recovery from SCI. To test this hypothesis, we examined the therapeutic potential of delayed AZM treatment on locomotor, sensory, and anatomical recovery. We administered AZM beginning 30-min, 3-h, or 24-h following contusion SCI in female mice, and then daily for 7 days. AZM administration beginning 30-min and 3-h post-injury improved locomotor recovery with increased stepping function relative to vehicle controls. Further, delaying treatment for 30-min after SCI significantly reduced lesion pathology. Initiating AZM treatment 24-h post-injury was not therapeutically effective. Regardless of the timing of the initial treatment, AZM did not statistically reduce the development of neuropathic pain (mechanical allodynia) nor increase neuron survival. Collectively, these results add to a growing body of evidence supporting AZM's translational potential as a therapeutic agent for SCI and other neuroinflammatory conditions in which patients currently have very few options.
Insights
Early administration of azithromycin (AZM) after spinal cord injury (SCI) improves locomotor function and reduces lesion severity. Delayed treatment is less effective, highlighting the importance of timely intervention for potential SCI therapy.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Spinal cord injury (SCI) leads to macrophage infiltration and pro-inflammatory responses, contributing to neurodegeneration.
- Azithromycin (AZM), an FDA-approved antibiotic, exhibits immunomodulatory effects beneficial in inflammatory conditions.
- Previous studies indicated AZM reduces pro-inflammatory macrophage activation post-SCI and improves recovery with combined pre- and post-injury treatment.
Purpose of the Study:
- To investigate the therapeutic potential of delayed azithromycin (AZM) treatment on recovery from spinal cord injury (SCI).
- To evaluate the impact of AZM timing on locomotor, sensory, and anatomical recovery after SCI.
- To assess AZM's efficacy in mitigating neuropathic pain and enhancing neuron survival post-SCI.
Main Methods:
- Female mice with contusion SCI received AZM daily for 7 days, starting at 30 minutes, 3 hours, or 24 hours post-injury.
- Locomotor function, sensory deficits (neuropathic pain), and lesion pathology were assessed.
- Neuron survival was evaluated to determine the drug's neuroprotective effects.
Main Results:
- AZM administration initiated at 30 minutes and 3 hours post-SCI significantly improved locomotor recovery and stepping function.
- Early AZM treatment (30 minutes post-injury) notably reduced lesion pathology.
- Treatment initiated 24 hours post-injury showed no therapeutic benefit.
- AZM did not significantly reduce neuropathic pain or increase neuron survival, irrespective of treatment timing.
Conclusions:
- Delayed azithromycin treatment shows therapeutic potential for spinal cord injury (SCI), particularly when administered early post-injury.
- Timely intervention with AZM can improve functional recovery and reduce lesion pathology after SCI.
- AZM demonstrates translational potential for treating SCI and other neuroinflammatory conditions with limited therapeutic options.
