Effects Of Change In Blood Brain Barrier Permeability On Microglia In Mouse Brain After Cerebral Ischemia

The blood-brain barrier is a natural barrier to the central nervous system.The permeability of the blood-brain barrier is changed during cerebral ischemia and reperfusion.Microglia are the immune cells in the central nervous system,and microglia in different brain regions have different morphology and functions.Microglia is very sensitive to the changes of the surrounding environment.Increase of the blood-brain barrier permeability can result in the accumulation of large numbers of free radicals and inflammatory factors in the mouse brain parenchyma.It still unclear that the effects of change in blood brain barrier permeability on microglia in mouse brain after cerebral ischemia.Here,the global cerebral ischemia-reperfusion models were established,and the permeability of blood-brain barrier was reduced by dapsone in the early stage of global cerebral ischemia-reperfusion.The proliferating microglia in different brain regions were labeled by immunofluorescence staining technique.The results showed that reduce the blood-brain barrier permeability can promote the proliferation of microglia in cerebral cortex,striatum,CA1 and PoDG.We also found that decreasing the permeability of blood-brain barrier could promote the expression of CSF1,IL34,IP10,BDNF and reduce the expression of CD11 b and TGF-? during the global cerebral ischemia-reperfusion by RT-PCR technique.The morphology of individual microglia was quantified in three-dimensional level by combined with the passive clarity technique,optical sectioning technique and three-dimensional reconstruction technique.Through analysis we found that microglial processes retained more branch structures after reducing the blood-brain barrier permeability during cerebral ischemia and reperfusion.This study demonstrated that reducing the permeability of the blood-brain barrier not only can promote the proliferation of microglia,but also affect the expression of BDNF,IP10,CD11 b and the morphology of microglia during global cerebral ischemia-reperfusion.These results provide a new theoretical basis for the clinical treatment of ischemia.Passive clarity technique combined with 3D reconstruction technique can analyze the spatial structure of microglia in many aspects,these new methods can be used to further analysis of the relationship between microglial morphology and function in pathological conditions.