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Updated: Aug 24, 2026
Procedures for Identifying Infectious Prions After Passage Through the Digestive System of an Avian Species
Published on: November 6, 2013
Passage of murine scrapie prion protein across the mouse vascular blood-brain barrier
William A Banks1, Michael L Niehoff, Celine Adessi
1GRECC, Veterans Affairs Medical Center-St. Louis and Division of Geriatrics, Department of Internal Medicine, Saint Louis University School of Medicine, 915 N. Grand Blvd., St. Louis, MO 63106, USA. bankswa@slu.edu
Abstract:
Prions are the infectious agents associated with transmissible spongiform encephalopathies and are composed mainly of a misfolded form of the endogenous prion protein. Prion protein must enter the brain to produce disease. Previous work has emphasized various mechanisms which partially bypass the blood-brain barrier (BBB). Here, we used the brain perfusion method to directly assess the ability of mouse scrapie protein (PrP(SC)) to cross the mouse BBB independent of the influences of neural pathways or circulating immune cells. We found that PrP(SC) oligomers rapidly crossed the BBB without disrupting it with a unidirectional influx rate of about 4.4microl/g-min. HPLC and capillary depletion confirmed that PrP(SC) crossed the entire width of the capillary wall to enter brain parenchyma. PrP(SC) also entered the cerebrospinal fluid (CSF) compartment. These results show that a prion protein can cross the intact BBB to enter both the parenchymal and CSF compartments of the brain.
Insights
Prion protein (PrP(SC)) can cross the intact blood-brain barrier (BBB) into the brain. This study demonstrates direct entry of infectious prions into brain parenchyma and cerebrospinal fluid.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Prions cause transmissible spongiform encephalopathies.
- Prion protein entry into the brain is necessary for disease.
- Previous studies suggested partial bypass of the blood-brain barrier (BBB).
Purpose of the Study:
- To directly assess if mouse scrapie protein (PrP(SC)) can cross the mouse BBB.
- To evaluate PrP(SC) BBB crossing independent of neural pathways or immune cells.
Main Methods:
- Brain perfusion method was utilized.
- High-performance liquid chromatography (HPLC) and capillary depletion were employed.
Main Results:
- PrP(SC) oligomers rapidly crossed the intact BBB without disruption.
- A unidirectional influx rate of approximately 4.4 microl/g-min was observed.
- PrP(SC) entered both brain parenchyma and the cerebrospinal fluid (CSF) compartment.
Conclusions:
- Prion protein can directly cross the intact blood-brain barrier.
- Entry occurs into both the brain's parenchymal and CSF compartments.
- This finding has implications for understanding prion disease pathogenesis.
