Grants and Contracts Details


Overall Objective: Our goal is to modulate the inflammatory response to spinal cord injury (SCI) in favor of an attenuated neutrophil influx and a polarized macrophage response that will favor post-SCI repair and improve recovery. Inflammation is a ubiquitous but poorly understood consequence of neurotrauma. Appreciation for both the reparative and pathological potential of activated immune cells (macrophages and neutrophils) has grown in recently years, however, the development of clinically-viable, immunomodulatory therapies that can harness their reparative potential while limiting pathology remains a critical challenge facing the SCI community. We have identified unique, immunomodulatory properties associated with azithromycin (AZM) treatment of SCI. This antibiotic is well tolerated in individuals with SCI, but there are no published reports examining AZM as a treatment for CNS injury. Through the completion of the specific aims outlined below we will gain mechanistic insight into the beneficial and harmful effects of neuroinflammation, as well as, establish important pre-clinical dose and timing parameters for translation of a potentially effective SCI therapy. Our overall hypothesis is that azithromycin will effectively modulate the inflammatory response after SCI with a clinically practical therapeutic window. Secondly, azithromycin treatment will improve neuroprotection, repair, and functional recovery after SCI. We will test these hypotheses utilizing a clinically-relevant, moderate (75kdyn) thoracic mouse contusion SCI model. Aim 1: To determine the dose-related efficacy of post-SCI administered AZM treatment in polarizing the inflammatory response to facilitate repair. AZM treatment at 3 different doses (dose 1, 2, 3), or vehicle control, will be given 30 minutes after SCI and then administered daily for the duration of the study. Flow cytometry will be used to assess neutrophil and macrophage infiltration at 1 and 7 days post-SCI (dpi) to encompass the peak phase of the neutrophil reaction (1 dpi) and the onset and peak phases of macrophage activation (1 and 7dpi respectively). Then macrophages will be isolated using FACS for phenotyping using customized gene array cards. Aim 2: To examine the efficacy and therapeutic window of the optimal dose of AZM (from Aim 1) to improve the locomotor recovery and tissue sparing during the first 28 days after moderate thoracic contusion SCI. A battery of behavioral, anatomical, and molecular assays will be used to determine the therapeutic window of post-SCI AZM treatment (begun 30min, 3hrs, or 24hrs post-SCI, then daily for 7days) on functional recovery and wound repair.
Effective start/end date1/1/1410/12/16


  • Craig H. Neilsen Foundation: $299,018.00


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