Cytofluorescence localization of adriamycin in the nervous system. IV. cellular uptake of the drug in peripheral nerve following various modes of injection to bypass the blood-nerve and the perifascicular barriers.

Adriamycin (Doxorubicin) is a powerful anthracyclic compound, which is widely used in the treatment of malignant diseases. In the rat a single systemic injection of the drug can induce pronounced lesions in peripheral ganglia, whereas in other parts of the peripheral nervous system (PNS) no changes have been reported. Since adriamycin can be directly traced in tissue sections by fluorescence microscopy it is very well suited for experimental studies on the relation between cytotoxic effects and distribution of the drug following various modes of administration. We have previously shown that after an intravenous (i.v.) injection there is an absence of adriamycin-induced nuclear fluorescence in the endoneurium of mouse sciatic nerve (Bigotte et al. 1982 b). This could either be due to barrier effects in endoneurial vessels and the perineurium or to a lacking capacity of the endoneurial cell population to take up and retain adriamycin. In the present study the blood-nerve and the perifascicular diffusion barriers were therefore bypassed by endoneurial microinjections of adriamycin. After this mode of administration, Schwann cells, endoneurial mast cells, endothelial cells, and pericytes became labeled. Experimental damage of these barriers induced by ligation of the nerve also resulted in a diffusion of the drug into the endoneurial area and labeling of the same cells. The absence of nuclear binding in the endoneurium of mouse sciatic nerves after i.v. injection of adriamycin is therefore most probably due to a low or absent passage of the drug from the blood into the endoneurium, i.e., a combined barrier action of endoneurial vessels and the perineurium. Other experiments with epineurial application of the drug showed that thin intramuscular (i.m.) nerve branches differ from the sciatic nerve fascicles in allowing small amounts of adriamycin to enter the endoneurium. The present observations are of interest since it can be assumed that patients receiving adriamycin as a cytostatic drug may suffer nerve lesions whenever defects of nerve barriers are present.