Suppression of activated microglia promotes survival and function of transplanted oligodendroglial progenitors.

To evaluate the functional consequence of microglial activation in vivo, oligodendroglial progenitors were transplanted into the spinal cord of Long Evans shaker, a myelin mutant rat in which myelin defects are associated with progressive microglial activation. Cells grafted into neonatal rats at the initiation of gliosis successfully myelinated axons. However, cells transplanted during peak microglial activation did not lead to myelination due to death of the grafted cells within 3 days after transplantation. Pretreatment of these animals with minocycline, a tetracycline derivative, resulted in cell survival and myelination by the grafted cells. In culture, minocycline did not affect the survival, proliferation, or differentiation of oligodendroglial progenitors. Hence, minocycline likely modulates the function of reactive glia in vivo to promote the survival and myelination of transplanted oligodendroglial progenitors.