The pathogenesis of transmissible spongiform encephalopathy: routes to the brain and the erection of therapeutic barricades

Classical and modern studies of the pathogenesis of transmissible spongiform encephalopathy are reviewed with particular attention paid to recent investigations of the routes of neuroinvasion. In various experimental models, a heirarchy of paths to the brain includes direct neural transit from the site of infection, replication in the spleen and neural entry through the spinal cord, and hematogenous spread. Possible modes and sites of therapeutic intervention are suggested.