Sequential changes in the permeability of the blood-nerve barrier over the course of ricin neuronopathy in the rat.
We examined the sequential changes in the permeability of the BNB to a 4000-molecular-weight fluoresceinated dextran over an 18-week course of ricin neuronopathy. Neuronopathy was produced by injecting ricin into the tibial nerve of 18-day-old Long-Evans rats; permeability of the BNB in proximal sciatic nerve was evaluated by fluorescence microscopy 12 hours to 18 weeks post injection. BNB breakdown occurred two days after ricin injection and continued to be present over the 18-week course of the experiment. Ultrastructural studies revealed that Wallerian-type axonal degeneration was present in proximal sciatic nerve one day post injection. The degeneration involved only a portion of the fibers and was unaccompanied by subsequent axonal regeneration or ricin-induced injury of Schwann cells, endothelial cells or perineurial cells. Immunocytochemical studies revealed that an increased number of endoneurial macrophages did not appear until after the BNB breakdown. We conclude that (1) breakdown of the BNB occurs early and is longlasting in ricin-induced neuronopathy; (2) the BNB breakdown is a consequence of ricin-induced axonal degeneration and is independent of regenerating axons, a systemic toxic effect of ricin on the BNB, or an influx of macrophages; and (3) toxicant-induced degeneration of less than half of the fibers in a nerve is sufficient to cause a localized, persistent breakdown of the BNB.
Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27599-7525.
T W
TW
Bouldin
T S
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Earnhardt
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ND
Goines
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012276:Ricin / Q000633:toxicity*; D012584:Sciatic Nerve / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors
D003911:Dextrans; D005452:Fluoresceins; D005456:Fluorescent Dyes; C015219:fluorescein isothiocyanate dextran; D012276:Ricin; D016650:Fluorescein-5-isothiocyanate