Relationship Between Chemotaxis Of Brain Microglial Cells And Biological Characteristics Of Gliomas

Microglia is one of the important non-neoplastic elements of cerebral glioma(CG).The interaction of glioma and microglia promotes tumor progression.However,the spatiotemporal heterogeneity of the microglia in the context of glioma remains uncertain.In this study,CG model was built with C6 cell implantation in 28 SD rat to investigate the spatiotemporal heterogeneity in the microglial colonization during the tumor progression.T2 wighted Magnetic Resonance Imaging(T2WI)was conducted at the post-operative day7,9,12,14,16,18,22,23 and 24 after the model built-up,after which the HE and immunofluorescent staining of the entire brain section were prepared.Nine regions of interest(ROI)were defined within the tumor,the peritumoral and the contralesional areas on the HE sections with the largest tumor expansion.SIFT(Scale-invariant feature transform)algorithm was used to register and fuse the HE-immunofluorescent image pairs.ROIs defined on the HE sections were then translated to the immunofluorescence images.The averaged signal intensity was measured on the image of T2WI with the largest tumor diameter(D).Mean density(MD)of the microglia in the ROIs on the immunofluorescent images were measured for each ROI.The dependency of the abovementioned measurements on the time after C6 cell implantation(T)was estimated using mathematical modeling.MD in the tumor ROI was significantly larger than those of the rest ROIs(p<0.001).MD significantly increased with T and D that best fit to binomial(R~2=0.91,F=129.49,p<0.001)and linear functions(R~2=0.71,F=66.10,p<0.001),respectively,for all the ROIs,with a more precipitous inclination in the tumor MD.The average signal intensity of the ROIs on T2WI were also found positively correlated with the tumor MD(R~2=0.80,F=45.45,p<0.001).These findings indicate that tumor formation of C6 glioma triggers extensive microglia activation in the tumor and the non-neoplastic brain tissue,necessitating the assessment of microglia in both the local and global scales in performing the aggressiveness characterization and treatment trials targeting microenvironment of cerebral glioma..