Figure 5.

(A) Light microscopic silver staining of rat brain following a 10-min internal carotid artery infusion of a conjugate of 5 nm gold (Au) and the OX26 MAb against the rat TfR. Prior to perfusion fixation of rat brain with 2% glutaraldehyde, the brain vasculature was cleared with a saline infusion. Magnification bars = 10 microns in (A) and 100 nm in (B). (B,C) Electron microscopy of rat brain; the OX26 MAb—gold conjugate is observed both bound to the endothelial luminal membrane (arrows, B), and entrapped within the intra-endothelia compartment within 100 nm endosomes (arrow in B). The TfRMAb-Au conjugate is observed exocytosed across the abluminal membrane into the brain interstitium (C). (A–C) are reproduced with permission from Bickel et al. (109). (D) Confocal microscopy of freshly isolated unfixed rat brain capillaries shows labeling of the BBB TfR on both the luminal and abluminal endothelial plasma membranes by the rhodamine labeled OX26 TfRMAb conjugated THLs. Endothelial membranes are purple and intra-endothelial cytoplasm is yellow. Panel D is reproduced with permission of Huwyler and Pardridge (110).