Figure 4.

Distribution of the CNS-specific IgG1 antibody 11C7 in the nasal mucosa after region-specific intranasal delivery (study 3). A total dose of 60 µg 11C7 per mouse was administered at the olfactory (B–D,G–I,L–N) and respiratory (E,J,O) regions. The vehicle control was administered at the olfactory region and displays background staining from endogenous murine IgGs in the nasal mucus (A), and the choroid plexus (F), which was not removed after transcardial perfusion. The region-specificity became obvious in an investigation of the upper nasal cavity with its ethmoid turbinates: while after administration at the olfactory region the antibody was detectable at the olfactory mucosa (B), and showed a time-dependent clearance (C,D), no elevated levels of IgG were observed at the ethmoid turbinates after administration at the respiratory region. Further, none of the animals from the respiratory delivery group displayed any signs of a CNS delivery of 11C7 (J,O). A rapid distribution to the subventricular zones (see arrowheads) of the ventricles was found (G), that lasted up to 20 h (H), but was undetectable after 48 h (I). In addition, 11C7 was observed diffusely (see asterisks) in the hippocampus shortly after administration (L). The diffuse pattern disappeared within 20 h (M) and after 48 h distinct cells (see arrowheads) and neuronal projections were observed (N), highly similar to what was reported from Nogo-A expression studies [43]. Scale bar, 100 µm.