Imatinib Ameliorates Neuroinflammation in a Rat Model of Multiple Sclerosis by Enhancing Blood-Brain Barrier Integrity and by Modulating the Peripheral Immune Response
Figure 4
Imatinib downregulates CCR2 expression in the CNS during EAE.
(A–D) IHC analysis of CCR2 expression (in brown) performed on paraffin embedded spinal cord cross-sections on day 10 p.i. (n = 8 rats/experimental group) and 14 p.i. (n = 5 rats/experimental group). On day 10 p.i. CCR2+ cells were clearly detectable in the lesions of the PBS rats (B), while they were not present in the imatinib group (A). On day 14 p.i., in contrast to the imatinib-treated, spinal cord tissue from the PBS group undergoing EAE harbored high amounts of CCR2+ cells located in the blood vessels and perivascularly. Scale bar, 150 µm (A–D). (E, F) IF performed on spinal cord tissue cross-sections of the rats injected with fluorescent tracer (dextran, red) on day 14 p.i. (n = 5 rats/experimental group; representative images shown). Visualization of CCR2 antibody staining (in green), nuclei visualization by DAPI (blue). CCR2+ cells here shown in the subpial region exhibiting dextran extravasation and pronounced cell infiltration in the PBS group vs. imatinib-treated spinal cord region with moderate cell infiltration lacking in CCR2+ cells (E). (G) IF analysis quantification in correlation with dextran extravasation. CNS of the imatinib-treated rats significantly downregulated CCR2 expression comparing to controls on day 14 p.i. Scale bar, 50 µm (E, F). Imatinib or PBS oral gavage was performed from day 5 p.i until the end of the experiment. Error bars, S.E.M. Statistics were calculated using the t-test and P values <0.05 were considered significant (P<0.05 = *, P<0.01 = **, P<0.001 = ***).