title: The vagus nerve as a conduit for neuroinvasion, a diagnostic tool, and a therapeutic pathway for transmissible spongiform encephalopathies, including variant Creutzfeld Jacob disease.
abstract: It is hypothesised that the vagus nerve (cranial nerve X) is an important conduit for infective neuroinvasion during the incubation of certain transmissible spongiform encephalopathies (TSEs) including scrapie in sheep, variant Creutzfeld Jacob disease in humans, chronic wasting disease in deer, and bovine spongiform encephalopathy in cattle. Presence of infection in the brainstem will disrupt normal function of this important region responsible for autonomic control of visceral function via the vagus nerve. It is proposed that physiological study of disrupted vagal function using techniques such as heart rate variability will indicate early, and ongoing, functional signs of infection even before levels of abnormal prion protein reach the thresholds currently used in tests for the presence of TSEs. It is further suggested that repeated measures of vagal function during treatment with experimental therapies will give a non-invasive, repeated measures index of drug efficacy. In addition, pharmaceutical interventions directed via the vagus nerve will bypass the blood brain barrier and take an anatomical route appropriate to the treatment of TSEs.
authors.affiliation: Division of Cardiovascular and Endocrine Sciences, The University of Manchester, Department of Anaesthesia, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. chris.pomfrett@manchester.ac.uk
authors.forename: Chris J D
authors.initials: CJ
authors.lastname: Pomfrett
authors.forename: David G
authors.initials: DG
authors.lastname: Glover
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Pollard
mesh_terms: D000818:Animals; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000635:transmission; D003670:Deer; D006801:Humans; D008954:Models, Biological; D017096:Prion Diseases / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000635:transmission; D011328:Prions / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D014630:Vagus Nerve / Q000502:physiology / Q000821:virology*
chemical_list: D011328:Prions