Pathogenesis of Experimental Scrapie

  1. Greg Bock Organizer and
  2. Joan Marsh
  1. Richard H. Kimberlin1 and
  2. Carol A. Walker2

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513613.ch4

Ciba Foundation Symposium 135 - Novel Infectious Agents and the Central Nervous System

Ciba Foundation Symposium 135 - Novel Infectious Agents and the Central Nervous System

How to Cite

Kimberlin, R. H. and Walker, C. A. (2007) Pathogenesis of Experimental Scrapie, in Ciba Foundation Symposium 135 - Novel Infectious Agents and the Central Nervous System (eds G. Bock and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513613.ch4

Author Information

  1. 1

    AFRC & MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK

  2. 2

    MRC Radiobiology Unit, Chilton, Didcot, OX11 ORD, UK

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471915126

Online ISBN: 9780470513613

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Keywords:

  • pathogenesis;
  • experimental scrapie;
  • lymphoreticular system (lrs);
  • visceral autonomic nerves;
  • cell-to-cell infection spread

Summary

Most of our understanding of the pathogenesis of the unconventional slow infections comes from studies of experimental scrapie in mice and hamsters. After injection by non-neural peripheral routes, pathogenesis necessarily involves the lymphoreticular system (LRS) before the central nervous system (CNS). Available evidence indicates haematogenous spread from the site of injection to the scrapie replication sites in the LRS; later, infection spreads along visceral autonomic nerves from the LRS to the thoracic spinal cord, and thence to brain. The cells in the LRS which are important to scrapie pathogenesis are long lived. Neuroinvasion and spread of infection within the CNS probably involve neuronal pathways. We suggest that disease develops after infection has reached certain clinical target areas in the CNS but only when scrapie replication there has caused sufficient functional damage. Restriction of the replication process in both LRS and CNS is indicated by the occurrence of plateau concentrations of infectivity, especially in some long incubation scrapie models. A remarkable feature of these is that both neuroinvasion and clinical disease occur long after infectivity plateaux have been reached in the LRS and CNS, respectively. We propose that the slowness of scrapie is related to (1) limitations of cell-to-cell spread of infection from LRS to CNS, and (2) limitations on spread between neurons, coupled with restrictions on replication in brain.