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

Autor: Thorsten R. Doeppner, Raluca Reitmeir, Ertugrul Kilic, Sabine I. Hagen, Dirk M. Hermann, Ayman ElAli, Marco Bacigaluppi, Ulkan Kilic, Josephine Herz, Anil Zechariah, Zeyun Guo, Barbara S. Reinboth, Stefano Pluchino
Rok vydání: 2012
Předmět:
Male
Vascular Endothelial Growth Factor A
Red nucleus
Anti-Inflammatory Agents
Medizin
Brain Edema
Functional Laterality
Mice
Axonal sprouting
chemistry.chemical_compound
Neuroinflammation
Neural Pathways
Red Nucleus
Cerebral Cortex
Neuronal Plasticity
Ischemic stroke
Hand Strength
Cerebral infarction
Dextrans
Infarction
Middle Cerebral Artery
Cerebral Infarction
Neuroprotection
Vascular endothelial growth factor
medicine.anatomical_structure
Neurology
Cerebral cortex
Cytokines
Ischemia
Biotin
inflammatory
Motor Activity
Article
lcsh:RC321-571
Organophosphorus Compounds
Organometallic Compounds
medicine
Animals
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Injections
Intraventricular
Brain plasticity
Pyramidal tracts
business.industry
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
Gene Expression Regulation
chemistry
Nerve Degeneration
business
Neuroscience
Zdroj: Neurobiology of Disease, Vol 45, Iss 3, Pp 1077-1085 (2012)
ISSN: 0969-9961
Popis: Vascular 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.
Databáze: OpenAIRE
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