Delayed Azithromycin Treatment Improves Recovery After Mouse Spinal Cord Injury

Timothy J. Kopper, Katelyn E. McFarlane, William M. Bailey, Michael B. Orr, Bei Zhang, John C. Gensel

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Article number490
JournalFrontiers in Cellular Neuroscience
Volume13
DOIs
StatePublished - Nov 6 2019

Bibliographical note

Funding Information:
We would like to thank Linda Simmerman for her assistance in acquiring images, Amy Effinger and Caitlin Seward for their technical assistance, and Dr. Joe Springer for sharing his equipment. Funding. This work was supported by the Craig H. Neilsen Foundation SCIRTS Pilot Grant (JG); National Institute of Neurological Disorders and Stroke (NINDS) R01NS091582 (JG), NINDS T32 NS077889 (TK), and NINDS F31 NS105443 (TK).

Publisher Copyright:
© Copyright © 2019 Kopper, McFarlane, Bailey, Orr, Zhang and Gensel.

Keywords

  • M1
  • M2
  • alternatively-activated
  • anti-inflammatory
  • microglia
  • monocyte
  • neuroinflammation
  • neuroprotection

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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