Blood borne transit of CJD from brain to gut at early stages of infection.
BACKGROUND
In Creutzfeldt-Jakob disease (CJD) and other related transmissible spongiform encephalopathies it is critical to understand the various pathways by which the infectious agent spreads to different organs.


METHODS
We injected a CJD agent into mice, either intracerebrally (ic) or intraperitoneally (ip) and monitored the progressive appearance of abnormal PrP in peripheral tissues over time.


RESULTS
Abnormal PrP was detected in lymphoreticular tissues of the gastrointestinal tract as early as 28 to 32 days after infection by both routes. This change persisted until the terminal stages of disease. In contrast, abnormal PrP was not detected in brain or spinal cord until 80 to 120 days after ic inoculation, or until 170 days after ip inoculation.


CONCLUSIONS
Brain lacks significant lymphatic drainage, and has little infectivity before 40 days, even after ic inoculation. Thus the infectious inoculum must spread to the gut by a vascular route, a direction opposite to that generally assumed. This interpretation is consistent with previous studies demonstrating white blood cell infectivity as well as perivascular PrP accumulations in CJD. Notably, enteric infection at early as well as later stages of disease, and regardless of the route of agent entry, implicates potential environmental spread by fecal matter.
Radebold
K
K
Section of Neuropathology, Yale Medical School, 310 Cedar St, New Haven, CT 06510, USA. laura.manuelidis@yale.edu
Chernyak
M
M
Martin
D
D
Manuelidis
L
L
D000818:Animals; D001921:Brain / Q000378:metabolism*; D007562:Creutzfeldt-Jakob Syndrome / Q000503:physiopathology*; D004064:Digestive System / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D018620:PrPSc Proteins / Q000032:analysis* / Q000378:metabolism
D018620:PrPSc Proteins