Minocycline promotes long-term survival of neuronal transplant in the brain by inhibiting late microglial activation and T-cell recruitment.
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.
Michel-Monigadon
Delphine
D
INSERM, UMR, Nantes, France.
Nerrière-Daguin
Véronique
V
Lévèque
Xavier
X
Plat
Martine
M
Venturi
Eric
E
Brachet
Philippe
P
Naveilhan
Philippe
P
Neveu
Isabelle
I
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
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