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Intracerebroventricularly delivered VEGF promotes contralesional corticorubral plasticity after focal cerebral ischemia via mechanisms involving anti-inflammatory actions

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dc.contributor.authorHerz, Josephine
dc.contributor.authorReitmeir, Raluca
dc.contributor.authorHagen, Sabine I.
dc.contributor.authorReinboth, Barbara S.
dc.contributor.authorGuo, Zeyun
dc.contributor.authorZechariah, Anil
dc.contributor.authorElAli, Ayman
dc.contributor.authorDoeppner, Thorsten R.
dc.contributor.authorBacigaluppi, Marco
dc.contributor.authorPluchino, Stefano
dc.contributor.authorKilic, Ulkan
dc.contributor.authorKilic, Ertugrul
dc.contributor.authorHermann, Dirk M.
dc.date.accessioned2020-10-22T18:38:12Z
dc.date.available2020-10-22T18:38:12Z
dc.date.issued2012-03-01T00:00:00Z
dc.description.abstractVascular endothelial growth factor (VEGF) has potent angiogenic and neuroprotective effects in the ischemic brain. Its effect on axonal plasticity and neurological recovery in the post-acute stroke phase was unknown. Using behavioral tests combined with anterograde tract tracing studies and with immunohistochemical and molecular biological experiments, we examined effects of a delayed i.c.v. delivery of recombinant human VEGF(165), starting 3 days after stroke, on functional neurological recovery, corticorubral plasticity and inflammatory brain responses in mice submitted to 30 min of middle cerebral artery occlusion. We herein show that the slowly progressive functional improvements of motor grip strength and coordination, which are induced by VEGF, are accompanied by enhanced sprouting of contralesional corticorubral fibres that branched off the pyramidal tract in order to cross the midline and innervate the ipsilesional parvocellular red nucleus. Infiltrates of CD45+ leukocytes were noticed in the ischemic striatum of vehicle-treated mice that closely corresponded to areas exhibiting Iba-1+ activated microglia. VEGF attenuated the CD45+ leukocyte infiltrates at 14 but not 30 days post ischemia and diminished the microglial activation. Notably, the VEGF-induced anti-inflammatory effect of VEGF was associated with a downregulation of a broad set of inflammatory cytokines and chemokines in both brain hemispheres. These data suggest a link between VEGFs immunosuppressive and plasticity-promoting actions that may be important for successful brain remodeling. Accordingly, growth factors with anti-inflammatory action may be promising therapeutics in the post-acute stroke phase. (C) 2011 Elsevier Inc. All rights reserved.
dc.identifier.citationHerz J., Reitmeir R., Hagen S. I. , Reinboth B. S. , Guo Z., Zechariah A., ElAli A., Doeppner T. R. , Bacigaluppi M., Pluchino S., et al., -Intracerebroventricularly delivered VEGF promotes contralesional corticorubral plasticity after focal cerebral ischemia via mechanisms involving anti-inflammatory actions-, NEUROBIOLOGY OF DISEASE, cilt.45, ss.1077-1085, 2012
dc.identifier.doi10.1016/j.nbd.2011.12.026
dc.identifier.pubmed
dc.identifier.scopus84856588450
dc.identifier.urihttp://hdl.handle.net/20.500.12645/24292
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0969996111004013
dc.identifier.wosWOS:000300519600025
dc.subjectinflammatory
dc.titleIntracerebroventricularly delivered VEGF promotes contralesional corticorubral plasticity after focal cerebral ischemia via mechanisms involving anti-inflammatory actions
dc.typeArticle
dspace.entity.typePublication
local.avesis.id9dbd26dd-b606-46a2-aed7-64f7309a0944
local.publication.isinternational1
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