title: Potentiation of neurite outgrowth and reduction of apoptosis by immunosuppressive agents: implications for neuronal injury and transplantation.
abstract: OBJECTIVE
  Immunosuppressive agents are believed to play a role in recovery from spinal cord injury, but the underlying mechanisms by which neuronal function is improved by these agents are poorly understood. In this study, the authors evaluate the effect of immunosuppressive medications on neurite outgrowth and cell survival after a pharmacologically induced injury.
  
  
  METHODS
  Differentiated human neuroblastoma SH-SY5Y cells were injured using the calcium agonist thapsigargin. After cellular injury, neurite outgrowth in the presence or absence of immunosuppressive agents was measured. Apoptosis was quantified with the aid of a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Neurite outgrowth was severely restricted following thapsigargin injury. Outgrowth was potentiated, however, by the addition of concentrations of 1 and 10 mM cyclosporin A in a dose-dependent fashion. Similarly, addition of 10 nM FK506 increased the percentage of neurites in the 20- to 40-micron range. A low dose (1 mM) of dexamethasone did not have a significant effect on neurite outgrowth, but a higher dose (10 mM) increased the percentage of neurites in the 10- to 45-micron range. These agents also lessened the degree of thapsigargin-induced apoptosis.
  
  
  CONCLUSIONS
  Immunosuppressive agents such as cyclosporin A, FK506, and dexamethasone can potentiate neurite outgrowth and protect against apoptotic cell death in a human postmitotic neuronal cell line. Such effects may have implications for lessening neuronal injury after neurotrauma, stroke, or neurodegeneration.
authors.affiliation: Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia 22908, USA. jps2f@virginia.edu
authors.forename: Jason
authors.initials: J
authors.lastname: Sheehan
authors.forename: Anne
authors.initials: A
authors.lastname: Eischeid
authors.forename: Randi
authors.initials: R
authors.lastname: Saunders
authors.forename: Nader
authors.initials: N
authors.lastname: Pouratian
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D019284:Thapsigargin; D003907:Dexamethasone; D016572:Cyclosporine; D016559:Tacrolimus