title: Pathogenesis of scrapie (strain 263K) in hamsters infected intracerebrally, intraperitoneally or intraocularly.
abstract: After intracerebral (i.c.) infection of hamsters, the 263K strain of scrapie replicated at a nearly constant exponential rate until clinical disease developed when titres in brain averaged 9.8 log10 LD50 i.c. units/g. After intraperitoneal infection, scrapie replication was first detected in spleen, then in thoracic spinal cord and finally in lumbar cord and brain. This pattern suggests that invasion of the central nervous system occurs by spread of infection along certain visceral autonomic nerves. Infectivity was detected in the thoracic cord only 3 to 4 weeks after infection (incubation period 16 weeks) indicating the exceptional neuroinvasiveness of this scrapie model. This observation and the failure of splenectomy to lengthen incubation period raises the possibility of direct infection of nerve tissue in the peritoneum and transport to the thoracic cord with minimal prior replication of scrapie agent extraneurally. After intraocular infection of the right eye, replication (or accumulation) of scrapie was detected in the right optic nerve and left superior colliculus, then in the right superior colliculus and finally in the left optic nerve and medulla. This pattern shows that scrapie infection can spread along nerves, possibly by intra-axonal transport. The duration of agent replication in brain (between detectable onset of replication and clinical disease) was shortest after intraperitoneal infection (51 to 58 days), longer after intracerebral infection (81 to 88 days) and longest after intraocular infection (greater than 121 days). These differences may reflect the relative efficiency of the neural pathways by which infectivity spreads from different sites of entry in the brain to the postulated 'clinical target areas'.
authors.forename: R H
authors.initials: RH
authors.lastname: Kimberlin
authors.forename: C A
authors.initials: CA
authors.lastname: Walker
mesh_terms: D000818:Animals; D001921:Brain / Q000382:microbiology; D006224:Cricetinae; D004261:DNA Replication; D005260:Female; D007700:Kinetics; D008647:Mesocricetus; D011328:Prions / Q000235:genetics / Q000472:pathogenicity*; D012608:Scrapie / Q000382:microbiology*; D013156:Splenectomy; D014779:Virus Replication
chemical_list: D011328:Prions