The Effect Of Microglial Ablation On Astrocytes And Neurons

Microglia are the major elements of the CNS cell populations, accounting for 5%-20% of glial cells in the CNS of rodents. As specialized immunocompetent cells of the CNS, they play an essential role in maintaining homeostasis of CNS tissue. Under pathological conditions, microglia are activated rapidly and proliferate surrounding the site of injury. Here we combined CX3CR1CreER/+:R26iDTR/+transgenic mice with photothrombotic stroke model. We investigated the proliferation of newborn microglia after rapid ablation, and analyzed the dynamics of activated microglia and astrocytes after ischemic lesion. We also studied the neuronal death and neuronal survival after stroke.The R26iDTR/+transgenic mice carrying Rosa26-stop-DTR alleles were crossed to CX3CRlCreER mice, which express tamoxifen-inducible Cre recombinase in microglia. A selective microglia-death system was constructed by treating the animals with tamoxifen and diphtheria toxin (DT). CX3CRlCreER/+:R26iDTO/+transgenic mice expressed the diphtheria toxin receptor (DTR) and were highly sensitive to diphtheria toxin. We found a 90.7% decrease in the number of Ibal immunoreactive cells in transgenic mice treated with tamoxifen and DT. The number of microglia gradually increased and returned into normal levels within a few weeks. Our results suggested that newborn microglia were derived from proliferation of resident microglia. The ablation of microglia contributed to an acute expansion of astrocyte population without affecting the number of neurons. After stroke, there was an increase in the number of reactive astrocytes and degenerational neurons. The dramatic changes on microglia didn’t affect the structural integrity of brain, but could exert deleterious effect under stroke. Accordance with specific functional states of microglia, these findings provided some insights into therapeutic approaches of stroke.