Delivery of transferrin and immunoglobulins to the ventricular system of the rat.

Abstract

Human transferrin, non-immune IgG (Ni-IgG), and anti-transferrin receptor IgG2a antibody (OX26) were injected intracerebroventricularly (icv) into the lateral cerebral ventricle of adult and 7-day postnatal (P7) rats. Brain distributions were detected with immunohistochemistry. In adult rats, within 10 min of injecting 1.25 nmol of human transferrin and Ni-IgG, the proteins were detected intracellularly in the vicinity of the ventricular system, in ependymal cells, neurons and glia. Choroid plexus epithelial cells also were labeled. On the pial surface, the proteins were observed in meninges, and intracellularly in leptomeningeal cells. The proteins were detectable in close association with the ventricular wall and the meninges up to approximately 4 hr after the injection. Neuronal human transferrin-immunoreactivity (IR) was observed in cells in close proximity to the ventricular system and subarachnoid space, e.g., neurons of the medial habenular nucleus, hippocampal cortex, and cerebellar cortex. By 24 hr after injection, these proteins were absent. Injection of 0.03 nmol human transferrin, Ni-IgG, or OX26 resulted in labeling of ependymal cells but not periventricular neurons or glia. In P7 rats, prominent labeling was seen irrespective of the injected molecule or dose. Likewise, the labeling of the neurons and glia distant from the ventricle or the pial surface was, however, much higher than in the adult. The proteins were detectable diffusely in the brain parenchyma even 24 hr after injection. The results are discussed with emphasis on whether icv injection of transferrin and OX26 can be used for targeting transferrin receptor-containing neurons.