Ki20227 Influences The Morphology Of Microglia And Neurons Through Inhibition Of CSF1R In Mice During Global Ischemia

The stroke causes serious damage to people's health.Ischemic stroke is a type of acute cerebrovascular incidence in which blood supply obstacles in the brain caused by various reasons damage neurons,microglia and surrounding vessels due to focal cerebral ischemia.The corresponding neurologic impairments include hemiplegia,aphasias,the cognitive and language impairments.At present,the main treatment for stroke is focused on improving the plasticity of neural circuits or on their repairing through multiple mechanisms.The new method should focus on complexity of the connections among multiple cells as well as cell survival pathways in the tissue repair process.After the stroke,microglia together with endothelial cells and other inducing factors,take part in the renovation of damaged tissues.As immunological competent cells in the brain,microglia can respond rapidly after the stroke.Under different physiologic and pathologic conditions,they have different functions.But there is still much debate as to their function after the stroke currently.Microglia may exert positive or negative effect on the neurons.At present,however,their effects after the stroke,along with the regulatory mechanism of microglial proliferation,are still unclear.In present study,we investigated the effect of Ki20227 on microglia and neurons,and whether microglia can improve the survival of neurons after global ischemia.This research is based on the experiment on the transgenic mice whose microglia can specifically express the green fluorescent proteins.Microglia were intervened with by inhibiting colony-stimulating factor 1 receptor(CSF1R)with Ki20227 and a global ischemic stroke model was established.Using two-photon transcranial imaging technique,the immunohistochemical staining technique,fluorescence microscopy,fluorescence quantitative polymerase chain reaction,and the behavioral testing,this research tries to reveal the influence of microglia on neurons after the stroke and to tentatively explore the regulatory mechanism of microglial proliferation.BrdU(5-Bromo-2-deoxy Uridine)staining demonstrated that microglia proliferated after stroke,and the results showed that stroke caused the abnormal expression of cytokines in the microglia,the reduction in the number of neurons,and the decline in the density of dendritic spines in cortex and hippocampus.In addition,stroke also resulted in behavior abnormality.In the meantime,the inhibition of CSF1 R by Ki20227 led to a decrease in the number of microglia and cell processes,and reduction in proliferative microglia.The relevant cytokines were also abnormally expressed.In addition,the density of neurons and dendritic spines declined,the expression level of synaptic molecules decreased and abnormal behaviors occured.To sum up,the results revealed that the morphology of the microglia,the density of microglia populations,and the expression of relevant cytokines were closely related to CSF1 R.Microglia may have a protective role for neurons after global ischemia.