Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-43322
Reitmeir, R; Kilic, E; Kilic, U; Bacigaluppi, M; ElAli, A; Salani, G; Pluchino, S; Gassmann, M; Hermann, D M (2011). Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity. Brain: A Journal of Neurology, 134(Pt .1):84-99.
The promotion of post-ischaemic motor recovery remains a major challenge in clinical neurology. Recently, plasticity-promoting effects have been described for the growth factor erythropoietin in animal models of neurodegenerative diseases. To elucidate erythropoietin's effects in the post-acute ischaemic brain, we examined how this growth factor influences functional neurological recovery, perilesional tissue remodelling and axonal sprouting of the corticorubral and corticobulbar tracts, when administered intra-cerebroventricularly starting 3 days after 30 min of middle cerebral artery occlusion. Erythropoietin administered at 10 IU/day (but not at 1 IU/day), increased grip strength of the contralesional paretic forelimb and improved motor coordination without influencing spontaneous locomotor activity and exploration behaviour. Neurological recovery by erythropoietin was associated with structural remodelling of ischaemic brain tissue, reflected by enhanced neuronal survival, increased angiogenesis and decreased reactive astrogliosis that resulted in reduced scar formation. Enhanced axonal sprouting from the ipsilesional pyramidal tract into the brainstem was observed in vehicle-treated ischaemic compared with non-ischaemic animals, as shown by injection of dextran amines into both motor cortices. Despite successful remodelling of the perilesional tissue, erythropoietin enhanced axonal sprouting of the contralesional, but not ipsilesional pyramidal tract at the level of the red and facial nuclei. Moreover, molecular biological and histochemical studies revealed broad anti-inflammatory effects of erythropoietin in both hemispheres together with expression changes of plasticity-related molecules that facilitated contralesional axonal growth. Our study establishes a plasticity-promoting effect of erythropoietin after stroke, indicating that erythropoietin acts via recruitment of contralesional rather than of ipsilesional pyramidal tract projections.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Integrative Human Physiology|
05 Vetsuisse Faculty > Institute of Veterinary Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||25 Jan 2011 16:28|
|Last Modified:||27 Nov 2013 19:38|
|Publisher:||Oxford University Press|
|Additional Information:||This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Brain following peer review. The definitive publisher-authenticated version 134(Pt 1):84-99 is available online at: http://brain.oxfordjournals.org/content/134/1/84.long|
|Citations:||Web of Science®. Times Cited: 24|
Scopus®. Citation Count: 28
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