Effect of CCR2 drug inhibition on the histopathological features of sm-EAN.
Representative digital indirect fluorescent immunohistochemistry photomicrographs of 10 μm frozen acetone fixed, axial sciatic nerve sections show disorganized or reduced S100β staining intensity indicative of demyelination (double white asterisk) associated with or without mononuclear cell infiltrates in Vehicle (A) and human IVIg treated (I) mice compared to the uniformly intense honeycomb appearance observed in CCR2 inhibitor (CCR2 INB) treated mice (E). The thin honeycomb background appearance seen in several regions of human IVIg treated mouse sections may also reflect early remyelination. Qualitative analyses suggest a reduction in large and small myelinated axon density in vehicle controls, associated with foci of mononuclear cells in some instances (white asterisk; B) compared to CCR2INB (F) and human IVIg treated (J) mice based on heavy chain neurofilament [NF-H] staining. Focal infiltration of F4/80+ monocytes/macrophages (white arrows), the predominant leukocyte subpopulation in sm-EAN, is seen in Vehicle controls (C). Fewer foci are seen following CCR2INB (G) and IVIg (K) treatment. Similarly, scattered foci of CD3+ T cells (white arrows) seen in Vehicle-treated controls (D) become less prevalent following CCR2INB (H) and IVIg (L) treatment. Fewer infiltrated mononuclear cells are observed with CCR2INB treatment compared to IVIg treatment. Cells are detected by the DAPI nuclear stain in all images. Scale bar = 100 μm.