Article
Prevention of global brain atrophy after unilateral parietal cryolesion by early neuroprotective treatment with erythropoietin
Prävention globaler Hirnatrophie nach parietaler Kryoläsion durch einen frühen neuroprotektiven Therapieansatz mit Erythropoietin
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Published: | May 8, 2006 |
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Objective: In humans, neurotrauma is suspected to cause brain atrophy and accelerate slowly progressive neurodegenerative disorders (Alzheimer's, Parkinson disease, schizophrenia). However, a direct link between brain injury and subsequent delayed global neurodegeneration has remained elusive. The issue we have addressed here is (i) whether or not a small localized lesion in the developing parietal cortex is sufficient to trigger global morphological changes in the mature brain, (ii) what the behavioral consequences of such a cascade might be, and (iii) whether a novel neuroprotective strategy involving recombinant erythropoietin (EPO) might prevent these changes.
Methods: Juvenile (4 week-old) mice were given a unilateral cryolesion of the right parietal cortex. High-resolution three-dimensional magnetic resonance imaging (MRI) and behavioral testing (hole board, elevated plus-maze, Rotarod, open-field, prepulse inhibition of startle, Morris water maze) were performed 3 and 9 months after lesioning. EPO (5 U/g, i.p.) or placebo (0.01 ml/g, i.p.) was administered immediately after setting of the lesion, and every other day for 14 days thereof.
Results: Significant reduction in brain volume and ventricular enlargement by in vivo 3D MRI were evident at 3 and 9 months after unilateral parietal cortical lesion. This brain atrophy was accompanied with distinct behavioral alterations and spatial learning deficits. EPO therapy prevented behavioral abnormalities, cognitive dysfunction and brain atrophy at 9 months after parietal cortical injury.
Conclusions: A discrete lesion to the parietal cortex of juvenile mice, i.e. during brain maturation, is by itself the primary cause of a global neurodegeneration, with significant changes in brain morphology and function upon long-term follow-up. The delayed global neurodegeneration can be efficiently counteracted by neuroprotective therapy.