Minocycline promotes long-term survival of neuronal transplant in the brain by inhibiting late microglial activation and T-cell recruitment
2010
Michel-Monigadon, D. | Nerriere-Daguin, V. | Leveque, X. | Plat, Martine | Venturi, Eric | Brachet, P. | Naveilhan, P. | Neveu, I. | UMR 643 ; Institut National de la Santé et de la Recherche Médicale (INSERM) | ITERT ; Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes) | Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN) | Physiologie de la reproduction et des comportements [Nouzilly] (PRC) ; Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS) | Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO) ; Institut National de la Recherche Agronomique (INRA) | ITERT | Université de Tours (UT)
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.
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