title: Minocycline promotes long-term survival of neuronal transplant in the brain by inhibiting late microglial activation and T-cell recruitment.
abstract: BACKGROUND
  Cell therapy in the brain is limited by the requirement of high doses of immunosuppressors that have harmful side effects, and often, it cannot prevent the ultimate rejection of the transplanted cells. Alternative treatments that replace or enable a reduction in the doses of usual immunosuppressors have to be found. In this regard, minocycline shows potential as therapeutic agent. This drug crosses the blood-brain barrier, has good safety records, and exhibits strong antiinflammatory effects.
  
  
  METHODS
  To study the impact of minocycline on the survival of intracerebral transplant, 400,000 porcine fetal neurons were transplanted into the striatum of rats treated daily with minocycline until sacrifice. Graft survival and immunologic reaction were evaluated by immunohistochemistry.
  
  
  RESULTS
  In the control groups, all the grafts were rejected at day 63, whereas healthy grafts exhibiting tyrosine hydroxylase neurons were observed in 40% of the treated rats. The low immunoreactivity for ED1 and R73 in treated rats when compared with the control groups suggests that minocycline promotes long-term survival of neuronal xenograft by inhibiting microglial activation and T-cell recruitment.
  
  
  CONCLUSIONS
  Our present data provide the first evidence of an effect of minocycline on the host immune response after neuronal transplantation into the brain. This observation raises new perspectives concerning the use of minocycline and provides basis for the development of safe and efficient immunosuppressive protocols for intracerebral transplantation.
authors.affiliation: INSERM, UMR, Nantes, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Michel-Monigadon
authors.forename: Véronique
authors.initials: V
authors.lastname: Nerrière-Daguin
authors.forename: Xavier
authors.initials: X
authors.lastname: Lévèque
authors.forename: Martine
authors.initials: M
authors.lastname: Plat
authors.forename: Eric
authors.initials: E
authors.lastname: Venturi
authors.forename: Philippe
authors.initials: P
authors.lastname: Brachet
authors.forename: Philippe
authors.initials: P
authors.lastname: Naveilhan
authors.forename: Isabelle
authors.initials: I
authors.lastname: Neveu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000276:immunology / Q000601:surgery; D039481:CD11b Antigen / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000196:embryology / Q000637:transplantation; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D034421:Sus scrofa; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D007166:Immunosuppressive Agents; D007381:Intermediate Filament Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C070305:neurofilament protein NF 70; D014446:Tyrosine 3-Monooxygenase; D008911:Minocycline