Effect of tunicamycin on the blood-brain barrier and on endothelial cells in vitro.

In guinea-pigs given 400 micrograms per kg of tunicamycin, the toxin responsible for the disease known as annual ryegrass toxicity, alterations in blood-brain barrier permeability were assessed with vascular tracers of differing particle size. The toxin caused loss of integrity of the barrier to the smallest diameter tracer, horseradish peroxidase, but the cerebral endothelium was able to retain larger particles of ferritin and colloidal gold in the circulation. The effect of tunicamycin on cultured endothelial cells was characterized by dose-dependent lethal damage to these cells, marked dilatation of cisternae of RER, severe cytoplasmic vacuolation and a reduced incidence of mitosis in surviving endothelial cells. It was concluded that tunicamycin is able to damage directly endothelial cells, with a resultant increase in cerebral vascular permeability.