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Environmental enrichment during the chronic phase after experimental stroke promotes functional recovery without synergistic effects of EphA4 targeted therapy.

Authors
  • de Boer, Antina1, 2
  • Storm, Annet1, 2
  • Gomez-Soler, Maricel3
  • Smolders, Silke1, 2
  • Rué, Laura1, 2
  • Poppe, Lindsay1, 2
  • B Pasquale, Elena3
  • Robberecht, Wim1, 4
  • Lemmens, Robin1, 2, 4
  • 1 Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, Leuven 3000, Belgium. , (Belgium)
  • 2 VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven 3000, Belgium. , (Belgium)
  • 3 Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • 4 Department of Neurology, University Hospitals Leuven, Leuven 3000, Belgium. , (Belgium)
Type
Published Article
Journal
Human Molecular Genetics
Publisher
Oxford University Press
Publication Date
Mar 13, 2020
Volume
29
Issue
4
Pages
605–617
Identifiers
DOI: 10.1093/hmg/ddz288
PMID: 31814004
Source
Medline
Language
English
License
Unknown

Abstract

Worldwide, stroke is the main cause of long-term adult disability. After the initial insult, most patients undergo a subacute period with intense plasticity and rapid functional improvements. This period is followed by a chronic phase where recovery reaches a plateau that is only partially modifiable by rehabilitation. After experimental stroke, various subacute rehabilitation paradigms improve recovery. However, in order to reach the best possible outcome, a combination of plasticity-promoting strategies and rehabilitation might be necessary. EphA4 is a negative axonal guidance regulator during development. After experimental stroke, reduced EphA4 levels improve functional outcome with similar beneficial effects upon the inhibition of EphA4 downstream targets. In this study, we assessed the effectiveness of a basic enriched environment in the chronic phase after photothrombotic stroke in mice as well as the therapeutic potential of EphA4 targeted therapy followed by rehabilitation. Our findings show that environmental enrichment in the chronic phase improves functional outcome up to 2 months post-stroke. Although EphA4 levels increase after experimental stroke, subacute EphA4 inhibition followed by environmental enrichment does not further increase recovery. In conclusion, we show that environmental enrichment during the chronic phase of stroke improves functional outcome in mice with no synergistic effects of the used EphA4 targeted therapy. © The Author(s) 2020. Published by Oxford University Press.

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