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Effect of tunicamycin on the blood-brain barrier and on endothelial cells in vitro
1Department of Agriculture and Rural Affairs, Veterinary Research Institute, Parkville, Victoria, Australia.
Abstract:
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.
Insights
Tunicamycin, a toxin causing annual ryegrass toxicity, damages brain endothelial cells and increases blood-brain barrier permeability in guinea-pigs. This toxin affects cell integrity, leading to leakage of small tracers but not larger ones.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Annual ryegrass toxicity is a disease affecting livestock.
- Tunicamycin is the causative toxin responsible for this condition.
- The blood-brain barrier (BBB) protects the central nervous system.
Purpose of the Study:
- To investigate the effects of tunicamycin on blood-brain barrier permeability.
- To assess the direct impact of tunicamycin on cerebral endothelial cells.
Main Methods:
- Guinea-pigs were administered tunicamycin (400 µg/kg).
- Vascular tracers of varying particle sizes (horseradish peroxidase, ferritin, colloidal gold) were used to assess BBB integrity.
- Cultured endothelial cells were exposed to tunicamycin to evaluate cellular damage.
Main Results:
- Tunicamycin increased BBB permeability to small tracers (horseradish peroxidase).
- The cerebral endothelium retained larger tracers (ferritin, colloidal gold).
- Tunicamycin caused dose-dependent lethal damage to endothelial cells, RER dilatation, vacuolation, and reduced mitosis.
Conclusions:
- Tunicamycin directly damages cerebral endothelial cells.
- This endothelial cell damage leads to increased cerebral vascular permeability.
- Tunicamycin is a key factor in the neurotoxicity of annual ryegrass.