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.