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Increased blood-brain barrier permeability in scrapie-infected mice
Abstract:
The present investigation was designed to study the ultrastructural integrity of the blood-brain barrier (BBB) in the cerebral microvasculature of scrapie-infected mice showing clinical illness. Cerebral microvessels from either IM, VM, or C57BL/6J mice, terminally affected with various strains of scrapie agent showed a focal leakage of horseradish peroxidase (HRP) in all agent-strain and mouse-strain combinations. This leakage was most pronounced in and near the primary site of agent inoculation, but was also observed in microvessels scattered throughout the brain. Cytochemical studies also revealed a redistribution of plasmalemma-bound alkaline phosphatase in the endothelial cells. In control mice, the enzymatic activity was mainly concentrated in the luminal plasmalemma, while in the scrapie-infected mice the activity also appeared in the abluminal side in the majority of microvessels. Our observations are evidence that the BBB of the mouse is altered in some way by the scrapie agent. Such an alteration may have important implications for human disease, since the scrapie agent is related to the group of "slow" viral infections, including kuru and Creutzfeldt-Jakob disease. Scrapie may also serve as an important model for the study of senile dementia of the Alzheimer type (SDAT).
Insights
Scrapie infection alters the blood-brain barrier (BBB) in mice, causing leakage and changes in enzyme activity. This finding is crucial for understanding related human diseases like Creutzfeldt-Jakob disease.
Area of Science:
- Neuroscience
- Pathology
- Infectious Diseases
Background:
- Scrapie is a transmissible spongiform encephalopathy affecting the central nervous system.
- The blood-brain barrier (BBB) protects the brain but its integrity in scrapie is not fully understood.
- Scrapie shares similarities with human prion diseases and Alzheimer's disease.
Purpose of the Study:
- To investigate the ultrastructural integrity of the BBB in scrapie-infected mice.
- To examine changes in cerebral microvasculature and endothelial cell function.
- To correlate BBB alterations with scrapie pathogenesis.
Main Methods:
- Utilized scrapie-infected mice (IM, VM, C57BL/6J) showing clinical illness.
- Employed horseradish peroxidase (HRP) leakage studies to assess BBB permeability.
- Conducted cytochemical analysis of plasmalemma-bound alkaline phosphatase in endothelial cells.
Main Results:
- Focal leakage of HRP was observed in cerebral microvessels of scrapie-infected mice.
- Leakage was most prominent near the inoculation site but also widespread.
- Alkaline phosphatase activity redistributed from luminal to abluminal sides of endothelial cells.
Conclusions:
- Scrapie agent significantly alters the BBB's ultrastructural integrity in mice.
- BBB dysfunction may play a role in scrapie pathogenesis.
- These findings have implications for understanding human prion diseases and neurodegenerative disorders like SDAT.