Global brain atrophy after unilateral parietal lesion and its prevention by erythropoietin.
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.
Sirén
Anna-Leena
AL
Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Radyushkin
Konstantin
K
Boretius
Susann
S
Kämmer
Daniel
D
Riechers
Claas-Christian
CC
Natt
Oliver
O
Sargin
Derya
D
Watanabe
Takashi
T
Sperling
Swetlana
S
Michaelis
Thomas
T
Price
Jack
J
Meyer
Barbara
B
Frahm
Jens
J
Ehrenreich
Hannelore
H
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
D004921:Erythropoietin