title: Spinal cord injury therapies in humans: an overview of current clinical trials and their potential effects on intrinsic CNS macrophages.
abstract: BACKGROUND
  Macrophage activation is a hallmark of spinal cord injury (SCI) pathology. CNS macrophages, derived from resident microglia and blood monocytes, are ubiquitous throughout the injured spinal cord, and respond to signals in the lesion environment by changing their phenotype and function. Depending on their phenotype and activation status, macrophages may initiate secondary injury mechanisms and/or promote CNS regeneration and repair.
  
  
  METHODS
  This review provides a comprehensive overview of current SCI clinical trials that are intended to promote neuroprotection, axon regeneration or cell replacement. None of these potential therapies were developed with the goal of influencing macrophage function; however, it is likely that each will have direct or indirect effects on CNS macrophages. The potential impact of each trial is discussed in the context of CNS macrophage biology.
  
  
  CONCLUSIONS
  Activation of CNS macrophages is an inevitable consequence of traumatic SCI. Given that these cells are exquisitely sensitive to changes in microenvironment, any intervention that affects tissue integrity and/or the composition of the cellular milieu will undoubtedly affect CNS macrophages. Thus, it is important to understand how current clinical trials will affect intrinsic CNS macrophages.
authors.affiliation: The Ohio State University College of Medicine, Center for Brain and Spinal Cord Repair, 795 Biomedical Research Tower, 460 West 12th Avenue, Columbus, OH 43210-1239, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Gensel
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Donnelly
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Popovich
mesh_terms: D017690:Cell Transplantation; D002986:Clinical Trials as Topic; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D058630:Spinal Cord Regeneration; D014945:Wound Healing
chemical_list: D018696:Neuroprotective Agents