title: Prion protein accumulation and neuroprotection in hypoxic brain damage.
abstract: The function of the normal conformational isoform of prion protein, PrP(C), remains unclear although lines of research have suggested a role in the cellular response to oxidative stress. Here we investigate the expression of PrP(C) in hypoxic brain tissues to examine whether PrP(C) is in part regulated by neuronal stress. Cases of adult cerebral ischemia and perinatal hypoxic-ischemic injury in humans were compared with control tissues. PrP(C) immunoreactivity accumulates within neuronal processes in the penumbra of hypoxic damage in adult brain, and within neuronal soma in cases of perinatal hypoxic-ischemic injury, and in situ hybridization analysis suggests an up-regulation of PrP mRNA during hypoxia. Rodents also showed an accumulation of PrP(C) in neuronal soma within the penumbra of ischemic lesions. Furthermore, the infarct size in PrP-null mice was significantly greater than in the wild type, supporting the proposed role for PrP(C) in the neuroprotective adaptive cellular response to hypoxic injury.
authors.affiliation: National Creutzfeldt-Jakob Disease Surveillance Unit and Pathology (Neuropathology), School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK. n.mclennan@ed.ac.uk
authors.forename: Neil F
authors.initials: NF
authors.lastname: McLennan
authors.forename: Paul M
authors.initials: PM
authors.lastname: Brennan
authors.forename: Alisdair
authors.initials: A
authors.lastname: McNeill
authors.forename: Ioan
authors.initials: I
authors.lastname: Davies
authors.forename: Andrew
authors.initials: A
authors.lastname: Fotheringham
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Rennison
authors.forename: Diane
authors.initials: D
authors.lastname: Ritchie
authors.forename: Francis
authors.initials: F
authors.lastname: Brannan
authors.forename: Mark W
authors.initials: MW
authors.lastname: Head
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.forename: Alun
authors.initials: A
authors.lastname: Williams
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Bell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D006579:Heterozygote; D006801:Humans; D002534:Hypoxia, Brain / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000378:metabolism*; D018621:PrPC Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018696:Neuroprotective Agents; D018621:PrPC Proteins