title: Global brain atrophy after unilateral parietal lesion and its prevention by erythropoietin.
abstract: In humans, neurotrauma is suspected to cause brain atrophy and accelerate slowly progressive neurodegenerative disorders, such as Alzheimer's disease or schizophrenia. However, a direct link between brain injury and subsequent delayed global neurodegeneration has remained elusive. Here we show that juvenile (4-week-old) mice that are given a discrete unilateral lesion of the parietal cortex, develop to adulthood without obvious clinical symptoms. However, when monitored 3 and 9 months after lesioning, using high-resolution three-dimensional MRI and behavioural testing, the same mice display global neurodegenerative changes. Surprisingly, erythropoietin, a haematopoietic growth factor with potent neuroprotective activity, prevents behavioural abnormalities, cognitive dysfunction and brain atrophy when given for 2 weeks after acute brain injury. This demonstrates that a localized brain lesion is a primary cause of delayed global neurodegeneration that can be efficiently counteracted by neuroprotection.
authors.affiliation: Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Anna-Leena
authors.initials: AL
authors.lastname: Sirén
authors.forename: Konstantin
authors.initials: K
authors.lastname: Radyushkin
authors.forename: Susann
authors.initials: S
authors.lastname: Boretius
authors.forename: Daniel
authors.initials: D
authors.lastname: Kämmer
authors.forename: Claas-Christian
authors.initials: CC
authors.lastname: Riechers
authors.forename: Oliver
authors.initials: O
authors.lastname: Natt
authors.forename: Derya
authors.initials: D
authors.lastname: Sargin
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Swetlana
authors.initials: S
authors.lastname: Sperling
authors.forename: Thomas
authors.initials: T
authors.lastname: Michaelis
authors.forename: Jack
authors.initials: J
authors.lastname: Price
authors.forename: Barbara
authors.initials: B
authors.lastname: Meyer
authors.forename: Jens
authors.initials: J
authors.lastname: Frahm
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
mesh_terms: D000208:Acute Disease; D000818:Animals; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D004921:Erythropoietin / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D009483:Neuropsychological Tests; D013997:Time Factors
chemical_list: D004921:Erythropoietin